rs746415437

Variant names:

• chr19-11059809-C-A
• NM_001387283.1:c.4788C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-11059809-C-A
• chr19-11059809-C-G
• chr19-11059809-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003072.5(SMARCA4):​c.4692C>A​(p.Ile1564Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,032 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.27

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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-4.27 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4788C>A	p.Ile1596Ile	synonymous_variant	Exon 34 of 36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4692C>A	p.Ile1564Ile	synonymous_variant	Exon 33 of 35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4788C>A	p.Ile1596Ile	synonymous_variant	Exon 34 of 36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4692C>A	p.Ile1564Ile	synonymous_variant	Exon 33 of 35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4698C>A	p.Ile1566Ile	synonymous_variant	Exon 33 of 35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4602C>A	p.Ile1534Ile	synonymous_variant	Exon 33 of 35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4602C>A	p.Ile1534Ile	synonymous_variant	Exon 32 of 34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4602C>A	p.Ile1534Ile	synonymous_variant	Exon 32 of 34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4599C>A	p.Ile1533Ile	synonymous_variant	Exon 33 of 35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.4113C>A	p.Ile1371Ile	synonymous_variant	Exon 30 of 32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3342C>A	p.Ile1114Ile	synonymous_variant	Exon 26 of 28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3324C>A	p.Ile1108Ile	synonymous_variant	Exon 25 of 27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.3186C>A	p.Ile1062Ile	synonymous_variant	Exon 25 of 27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.2952C>A	p.Ile984Ile	synonymous_variant	Exon 23 of 25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.756C>A	p.Ile252Ile	synonymous_variant	Exon 6 of 8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459032 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725652

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.056
DANN	Benign	0.49
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: chr19-11170485;