12-50098038-A-G

Position:

• chr12-50098038-A-G

Variant summary

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

The NM_003076.5(SMARCD1):​c.1393-676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,158 control chromosomes in the GnomAD database, including 9,038 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 (9038 hom., cov: 32)
• Consequence: SMARCD1 NM_003076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCD1	NM_003076.5	c.1393-676A>G		intron_variant		ENST00000394963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCD1	ENST00000394963.9	c.1393-676A>G		intron_variant		1	NM_003076.5	P1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47653 AN: 152040 Hom.: 9036 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.0753

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.313 AC: 47665 AN: 152158 Hom.: 9038 Cov.: 32 AF XY: 0.313 AC XY: 23304 AN XY: 74386

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.0753

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.341

Alfa AF: 0.335 Hom.: 1784

Bravo AF: 0.297

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs836177; hg19: chr12-50491821;