rs1555763825

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003072.5(SMARCA4):​c.1761+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SMARCA4
NM_003072.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 19-10996389-G-A is Benign according to our data. Variant chr19-10996389-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 470257.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCA4NM_001387283.1 linkc.1761+9G>A intron_variant Intron 10 of 35 ENST00000646693.2 NP_001374212.1
SMARCA4NM_003072.5 linkc.1761+9G>A intron_variant Intron 10 of 34 ENST00000344626.10 NP_003063.2 P51532-1A7E2E1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCA4ENST00000646693.2 linkc.1761+9G>A intron_variant Intron 10 of 35 NM_001387283.1 ENSP00000495368.1 Q9HBD4
SMARCA4ENST00000344626.10 linkc.1761+9G>A intron_variant Intron 10 of 34 1 NM_003072.5 ENSP00000343896.4 P51532-1
SMARCA4ENST00000643549.1 linkc.1761+9G>A intron_variant Intron 10 of 34 ENSP00000493975.1 A0A2R8Y4P4
SMARCA4ENST00000541122.6 linkc.1761+9G>A intron_variant Intron 11 of 34 5 ENSP00000445036.2 P51532-4
SMARCA4ENST00000643296.1 linkc.1761+9G>A intron_variant Intron 10 of 33 ENSP00000496635.1 P51532-4
SMARCA4ENST00000644737.1 linkc.1761+9G>A intron_variant Intron 10 of 33 ENSP00000495548.1 P51532-4
SMARCA4ENST00000589677.5 linkc.1761+9G>A intron_variant Intron 11 of 34 5 ENSP00000464778.1 P51532-3
SMARCA4ENST00000643995.1 linkc.1173+9G>A intron_variant Intron 7 of 31 ENSP00000496004.1 A0A2R8YGG3
SMARCA4ENST00000644963.1 linkc.405+9G>A intron_variant Intron 3 of 27 ENSP00000495599.1 A0A2R8YG32
SMARCA4ENST00000644065.1 linkc.489+9G>A intron_variant Intron 3 of 26 ENSP00000493615.1 A0A2R8Y440
SMARCA4ENST00000642350.1 linkc.249+9G>A intron_variant Intron 2 of 26 ENSP00000495355.1 A0A2R8Y6N0
SMARCA4ENST00000643857.1 linkc.114+9G>A intron_variant Intron 1 of 24 ENSP00000494159.1 A0A2R8Y526

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1
Jul 13, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
13
DANN
Benign
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1555763825; hg19: chr19-11107065; API