rs17001075

Variant names:

• chr19-10994917-A-C
• NM_001387283.1:c.1509A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10994917-A-C
• chr19-10994917-A-G
• chr19-10994917-A-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003072.5(SMARCA4):​c.1509A>C​(p.Ala503Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A503A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-3.98 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 10 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 9 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.1509A>C	p.Ala503Ala	synonymous_variant	Exon 10 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.921A>C	p.Ala307Ala	synonymous_variant	Exon 6 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.153A>C	p.Ala51Ala	synonymous_variant	Exon 2 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.237A>C	p.Ala79Ala	synonymous_variant	Exon 2 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.-4A>C		upstream_gene_variant				ENSP00000495355.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727196

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.29
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11105593;