chr12-50096316-C-G

Variant names:

• chr12-50096316-C-G
• rs836172
• NM_003076.5:c.1270-534C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Coffin-Siris syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000295262 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	NM_003076.5	MANE Select	c.1270-534C>G		intron	N/A	NP_003067.3
	SMARCD1	NM_139071.3		c.1269+1744C>G		intron	N/A	NP_620710.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	ENST00000394963.9	TSL:1 MANE Select	c.1270-534C>G		intron	N/A	ENSP00000378414.4
	SMARCD1	ENST00000381513.8	TSL:1	c.1269+1744C>G		intron	N/A	ENSP00000370924.4
	SMARCD1	ENST00000548573.5	TSL:5	c.664-534C>G		intron	N/A	ENSP00000448627.1

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

African (AFR) AF: 0.299 AC: 12375 AN: 41382

American (AMR) AF: 0.358 AC: 5459 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3470

East Asian (EAS) AF: 0.0801 AC: 415 AN: 5180

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4810

European-Finnish (FIN) AF: 0.450 AC: 4738 AN: 10528

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28443 AN: 67918

Other (OTH) AF: 0.381 AC: 804 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.5
DANN	Benign	0.62
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs836172; hg19: chr12-50490099;