rs3782323

Positions:

• chr12-50089138-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003076.5(SMARCD1):​c.771+501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,120 control chromosomes in the GnomAD database, including 8,586 homozygotes. 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: 𝑓 0.31 (8582 hom., cov: 32)
  • Exomes 𝑓: 0.23 (4 hom.)
• Consequence: SMARCD1 NM_003076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which 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 and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD1	NM_003076.5	c.771+501G>A		intron_variant		ENST00000394963.9	NP_003067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9	c.771+501G>A		intron_variant		1	NM_003076.5	ENSP00000378414	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47622 AN: 151914 Hom.: 8554 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.227 AC: 20 AN: 88 Hom.: 4 Cov.: 0 AF XY: 0.220 AC XY: 11 AN XY: 50

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.375

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.314 AC: 47684 AN: 152032 Hom.: 8582 Cov.: 32 AF XY: 0.322 AC XY: 23904 AN XY: 74308

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.304

Alfa AF: 0.256 Hom.: 3476

Bravo AF: 0.326

Asia WGS AF: 0.524 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs3782323; hg19: chr12-50482921;