rs836172

chr12-50096316-C-Gchr12-50096316-C-T

Variant summary

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

The NM_003076.5(SMARCD1):c.1270-534C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,852 control chromosomes in the GnomAD database, including 10,765 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 0.37 (10765 hom., cov: 31)
• Consequence: SMARCD1 NM_003076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCD1	NM_003076.5	c.1270-534C>G		intron_variant		ENST00000394963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCD1	ENST00000394963.9	c.1270-534C>G		intron_variant		1	NM_003076.5	P1
SMARCD1	ENST00000381513.8	c.1269+1744C>G		intron_variant		1
SMARCD1	ENST00000548573.5	c.664-534C>G		intron_variant		5
SMARCD1	ENST00000549274.1	c.68-534C>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55391 AN: 151734 Hom.: 10754 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55439 AN: 151852 Hom.: 10765 Cov.: 31 AF XY: 0.364 AC XY: 26983 AN XY: 74206

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.0801

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.381

Alfa AF: 0.241 Hom.: 575

Bravo AF: 0.357

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	7.5
Dann	Benign	0.62

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: rs836172; hg19: chr12-50490099;