rs1176344302

Variant names:

• chr19-10986897-A-G
• rs1176344302
• NM_001387283.1:c.761-8A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-10986897-A-G
• chr19-10986897-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003072.5(SMARCA4):​c.761-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,484 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003330
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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]

ACMG classification

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=-0.84).
• BP6: Variant 19-10986897-A-G is Benign according to our data. Variant chr19-10986897-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 537896.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 35	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 34	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 35		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 34	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 34			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.761-8A>G		splice_region_variant, intron_variant	Intron 5 of 34	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 33			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.761-8A>G		splice_region_variant, intron_variant	Intron 4 of 33			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.761-8A>G		splice_region_variant, intron_variant	Intron 5 of 34	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.173-8A>G		splice_region_variant, intron_variant	Intron 1 of 31			ENSP00000496004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250442 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135496

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450484 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Rhabdoid tumor predisposition syndrome 2 Benign:1

Oct 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs1176344302; hg19: chr19-11097573;