NM_001387283.1:c.3951+6C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001387283.1(SMARCA4):c.3951+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SMARCA4
NM_001387283.1 splice_region, intron

Scores

Splicing: ADA: 0.00004829

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.511

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-11034206-C-T is Benign according to our data. Variant chr19-11034206-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 470375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1 link	c.3951+6C>T		splice_region_variant, intron_variant	Intron 28 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5 link	c.3951+6C>T		splice_region_variant, intron_variant	Intron 28 of 34	ENST00000344626.10	NP_003063.2	P51532-1A7E2E1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMARCA4	ENST00000646693.2 link	c.3951+6C>T	splice_region_variant, intron_variant	Intron 28 of 35		NM_001387283.1	ENSP00000495368.1	Q9HBD4
SMARCA4	ENST00000344626.10 link	c.3951+6C>T	splice_region_variant, intron_variant	Intron 28 of 34	1	NM_003072.5	ENSP00000343896.4	P51532-1
SMARCA4	ENST00000643549.1 link	c.3852+6C>T	splice_region_variant, intron_variant	Intron 27 of 34			ENSP00000493975.1	A0A2R8Y4P4
SMARCA4	ENST00000541122.6 link	c.3852+6C>T	splice_region_variant, intron_variant	Intron 28 of 34	5		ENSP00000445036.2	P51532-4
SMARCA4	ENST00000643296.1 link	c.3852+6C>T	splice_region_variant, intron_variant	Intron 27 of 33			ENSP00000496635.1	P51532-4
SMARCA4	ENST00000644737.1 link	c.3852+6C>T	splice_region_variant, intron_variant	Intron 27 of 33			ENSP00000495548.1	P51532-4
SMARCA4	ENST00000589677.5 link	c.3852+6C>T	splice_region_variant, intron_variant	Intron 28 of 34	5		ENSP00000464778.1	P51532-3
SMARCA4	ENST00000643995.1 link	c.3363+6C>T	splice_region_variant, intron_variant	Intron 25 of 31			ENSP00000496004.1	A0A2R8YGG3
SMARCA4	ENST00000644963.1 link	c.2595+6C>T	splice_region_variant, intron_variant	Intron 21 of 27			ENSP00000495599.1	A0A2R8YG32
SMARCA4	ENST00000644065.1 link	c.2577+6C>T	splice_region_variant, intron_variant	Intron 20 of 26			ENSP00000493615.1	A0A2R8Y440
SMARCA4	ENST00000642350.1 link	c.2436+6C>T	splice_region_variant, intron_variant	Intron 20 of 26			ENSP00000495355.1	A0A2R8Y6N0
SMARCA4	ENST00000643857.1 link	c.2304+6C>T	splice_region_variant, intron_variant	Intron 19 of 24			ENSP00000494159.1	A0A2R8Y526
SMARCA4	ENST00000538456.4 link	c.108+6C>T	splice_region_variant, intron_variant	Intron 2 of 7	3		ENSP00000495197.1	A0A2R8YFK5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250658

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458406

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1109088

Other (OTH)

AF:

0.00

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 28, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Intellectual disability, autosomal dominant 16

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Rhabdoid tumor predisposition syndrome 2

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SMARCA4-related disorder

Benign:1

May 10, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.3

(source)

DANN

Benign

0.58

PhyloP100

0.51

PromoterAI

0.078

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000048

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over