19-11003321-G-T

Position:

chr19-11003321-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003072.5(SMARCA4):c.1944-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,611,630 control chromosomes in the GnomAD database, including 3,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 317 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3673 hom. )

Consequence

SMARCA4
NM_003072.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0440

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 links:

SMARCA4 (HGNC:):

SMARCA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-11003321-G-T is Benign according to our data. Variant chr19-11003321-G-T is described in ClinVar as [Benign]. Clinvar id is 257530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1 linkuse as main transcript	c.1944-19G>T		intron_variant		ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5 linkuse as main transcript	c.1944-19G>T		intron_variant		ENST00000344626.10	NP_003063.2	P51532-1A7E2E1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SMARCA4	ENST00000646693.2 linkuse as main transcript	c.1944-19G>T	intron_variant		NM_001387283.1	ENSP00000495368.1	Q9HBD4
SMARCA4	ENST00000344626.10 linkuse as main transcript	c.1944-19G>T	intron_variant	1	NM_003072.5	ENSP00000343896.4	P51532-1
SMARCA4	ENST00000643549.1 linkuse as main transcript	c.1944-19G>T	intron_variant			ENSP00000493975.1	A0A2R8Y4P4
SMARCA4	ENST00000541122.6 linkuse as main transcript	c.1944-19G>T	intron_variant	5		ENSP00000445036.2	P51532-4
SMARCA4	ENST00000643296.1 linkuse as main transcript	c.1944-19G>T	intron_variant			ENSP00000496635.1	P51532-4
SMARCA4	ENST00000644737.1 linkuse as main transcript	c.1944-19G>T	intron_variant			ENSP00000495548.1	P51532-4
SMARCA4	ENST00000589677.5 linkuse as main transcript	c.1944-19G>T	intron_variant	5		ENSP00000464778.1	P51532-3
SMARCA4	ENST00000643995.1 linkuse as main transcript	c.1356-19G>T	intron_variant			ENSP00000496004.1	A0A2R8YGG3
SMARCA4	ENST00000644963.1 linkuse as main transcript	c.588-19G>T	intron_variant			ENSP00000495599.1	A0A2R8YG32
SMARCA4	ENST00000644065.1 linkuse as main transcript	c.669-19G>T	intron_variant			ENSP00000493615.1	A0A2R8Y440
SMARCA4	ENST00000642350.1 linkuse as main transcript	c.429-19G>T	intron_variant			ENSP00000495355.1	A0A2R8Y6N0
SMARCA4	ENST00000643857.1 linkuse as main transcript	c.297-19G>T	intron_variant			ENSP00000494159.1	A0A2R8Y526

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

9307

AN:

152144

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0532

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0779

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0933

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0641

Gnomad OTH

AF:

0.0694

GnomAD3 exomes

AF:

0.0657

AC:

16526

AN:

251468

Hom.:

675

AF XY:

0.0695

AC XY:

9451

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.0309

Gnomad ASJ exome

AF:

0.0702

Gnomad EAS exome

AF:

0.0335

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0880

Gnomad NFE exome

AF:

0.0660

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0670

AC:

97803

AN:

1459368

Hom.:

3673

Cov.:

AF XY:

0.0686

AC XY:

49797

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.0528

Gnomad4 AMR exome

AF:

0.0332

Gnomad4 ASJ exome

AF:

0.0719

Gnomad4 EAS exome

AF:

0.0271

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0887

Gnomad4 NFE exome

AF:

0.0657

Gnomad4 OTH exome

AF:

0.0674

GnomAD4 genome

AF:

0.0612

AC:

9320

AN:

152262

Hom.:

317

Cov.:

AF XY:

0.0632

AC XY:

4704

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0532

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0779

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0933

Gnomad4 NFE

AF:

0.0641

Gnomad4 OTH

AF:

0.0705

Alfa

AF:

0.0402

Hom.:

Bravo

AF:

0.0560

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 01, 2016	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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Rhabdoid tumor predisposition syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2015

This alteration is classified as 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

-0.84

CADD

Benign

1.3

DANN

Benign

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over