rs11169270

Positions:

• chr12-50089249-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003076.5(SMARCD1):​c.771+612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,322 control chromosomes in the GnomAD database, including 5,318 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 0.23 (5315 hom., cov: 33)
  • Exomes 𝑓: 0.28 (3 hom.)
• Consequence: SMARCD1 NM_003076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852

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]

SMARCD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD1	NM_003076.5	c.771+612G>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+612G>A		intron_variant		1	NM_003076.5	ENSP00000378414.4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34882 AN: 152116 Hom.: 5318 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.00807

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.284 AC: 25 AN: 88 Hom.: 3 Cov.: 0 AF XY: 0.333 AC XY: 10 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.229 AC: 34870 AN: 152234 Hom.: 5315 Cov.: 33 AF XY: 0.226 AC XY: 16783 AN XY: 74410

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.226

Alfa AF: 0.290 Hom.: 1810

Bravo AF: 0.208

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.65

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: rs11169270; hg19: chr12-50483032;