chr19-11060148-G-C

Position:

• chr19-11060148-G-C

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.4872G>C​(p.Pro1624Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,842 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: 7.1e-7 (0 hom.)
• Consequence: SMARCA4 NM_003072.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.46

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 (HGNC:):

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=-0.73).
• BP7: Synonymous conserved (PhyloP=-6.46 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA4	NM_001387283.1	c.4968G>C	p.Pro1656Pro	synonymous_variant	35/36	ENST00000646693.2	NP_001374212.1
SMARCA4	NM_003072.5	c.4872G>C	p.Pro1624Pro	synonymous_variant	34/35	ENST00000344626.10	NP_003063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA4	ENST00000646693.2	c.4968G>C	p.Pro1656Pro	synonymous_variant	35/36		NM_001387283.1	ENSP00000495368.1
SMARCA4	ENST00000344626.10	c.4872G>C	p.Pro1624Pro	synonymous_variant	34/35	1	NM_003072.5	ENSP00000343896.4
SMARCA4	ENST00000643549.1	c.4878G>C	p.Pro1626Pro	synonymous_variant	34/35			ENSP00000493975.1
SMARCA4	ENST00000541122.6	c.4782G>C	p.Pro1594Pro	synonymous_variant	34/35	5		ENSP00000445036.2
SMARCA4	ENST00000643296.1	c.4782G>C	p.Pro1594Pro	synonymous_variant	33/34			ENSP00000496635.1
SMARCA4	ENST00000644737.1	c.4782G>C	p.Pro1594Pro	synonymous_variant	33/34			ENSP00000495548.1
SMARCA4	ENST00000589677.5	c.4779G>C	p.Pro1593Pro	synonymous_variant	34/35	5		ENSP00000464778.1
SMARCA4	ENST00000643995.1	c.4293G>C	p.Pro1431Pro	synonymous_variant	31/32			ENSP00000496004.1
SMARCA4	ENST00000644963.1	c.3522G>C	p.Pro1174Pro	synonymous_variant	27/28			ENSP00000495599.1
SMARCA4	ENST00000644065.1	c.3504G>C	p.Pro1168Pro	synonymous_variant	26/27			ENSP00000493615.1
SMARCA4	ENST00000642350.1	c.3366G>C	p.Pro1122Pro	synonymous_variant	26/27			ENSP00000495355.1
SMARCA4	ENST00000643857.1	c.3132G>C	p.Pro1044Pro	synonymous_variant	24/25			ENSP00000494159.1
SMARCA4	ENST00000538456.4	c.936G>C	p.Pro312Pro	synonymous_variant	7/8	3		ENSP00000495197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398842 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 689966

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.033
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11170824;