rs772356536

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_001387283.1(SMARCA4):c.2016G>A(p.Glu672Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SMARCA4
NM_001387283.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0100

Publications

1 publications found

Variant links:

Genes affected

SMARCA4 (HGNC:11100): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Mutations in this gene cause rhabdoid tumor predisposition syndrome type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

SMARCA4 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
intellectual disability, autosomal dominant 16
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
rhabdoid tumor predisposition syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
uterine corpus sarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
familial rhabdoid tumor
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SMARCA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 19-11007916-G-A is Benign according to our data. Variant chr19-11007916-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1784476.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000329 (5/152100) while in subpopulation AMR AF = 0.000328 (5/15260). AF 95% confidence interval is 0.000129. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 35	ENST00000344626.10	NP_003063.2	P51532-1A7E2E1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMARCA4	ENST00000646693.2 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 36		NM_001387283.1	ENSP00000495368.1	Q9HBD4
SMARCA4	ENST00000344626.10 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 35	1	NM_003072.5	ENSP00000343896.4	P51532-1
SMARCA4	ENST00000643549.1 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 35			ENSP00000493975.1	A0A2R8Y4P4
SMARCA4	ENST00000541122.6 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 15 of 35	5		ENSP00000445036.2	P51532-4
SMARCA4	ENST00000643296.1 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 34			ENSP00000496635.1	P51532-4
SMARCA4	ENST00000644737.1 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 14 of 34			ENSP00000495548.1	P51532-4
SMARCA4	ENST00000589677.5 link	c.2016G>A	p.Glu672Glu	synonymous_variant	Exon 15 of 35	5		ENSP00000464778.1	P51532-3
SMARCA4	ENST00000643995.1 link	c.1428G>A	p.Glu476Glu	synonymous_variant	Exon 11 of 32			ENSP00000496004.1	A0A2R8YGG3
SMARCA4	ENST00000644963.1 link	c.660G>A	p.Glu220Glu	synonymous_variant	Exon 7 of 28			ENSP00000495599.1	A0A2R8YG32
SMARCA4	ENST00000644065.1 link	c.741G>A	p.Glu247Glu	synonymous_variant	Exon 7 of 27			ENSP00000493615.1	A0A2R8Y440
SMARCA4	ENST00000642350.1 link	c.501G>A	p.Glu167Glu	synonymous_variant	Exon 6 of 27			ENSP00000495355.1	A0A2R8Y6N0
SMARCA4	ENST00000643857.1 link	c.369G>A	p.Glu123Glu	synonymous_variant	Exon 5 of 25			ENSP00000494159.1	A0A2R8Y526

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250282

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726912

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000895

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111698

Other (OTH)

AF:

0.00

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.000328

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000907

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:1

Feb 18, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.5

(source)

DANN

Benign

0.82

PhyloP100

-0.010

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over