rs836177

Variant names:

• chr12-50098038-A-G
• rs836177
• NM_003076.5:c.1393-676A>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.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
• Publications: 10 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
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	NM_003076.5	MANE Select	c.1393-676A>G		intron	N/A	NP_003067.3
	SMARCD1	NM_139071.3		c.1270-676A>G		intron	N/A	NP_620710.2	Q96GM5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD1	ENST00000394963.9	TSL:1 MANE Select	c.1393-676A>G		intron	N/A	ENSP00000378414.4	Q96GM5-1
	SMARCD1	ENST00000381513.8	TSL:1	c.1270-676A>G		intron	N/A	ENSP00000370924.4	Q96GM5-2
	SMARCD1	ENST00000915409.1		c.1420-676A>G		intron	N/A	ENSP00000585468.1

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

African (AFR) AF: 0.122 AC: 5069 AN: 41548

American (AMR) AF: 0.336 AC: 5136 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3470

East Asian (EAS) AF: 0.0753 AC: 391 AN: 5192

South Asian (SAS) AF: 0.213 AC: 1028 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4743 AN: 10568

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28422 AN: 67982

Other (OTH) AF: 0.341 AC: 719 AN: 2110

Alfa AF: 0.329 Hom.: 1793

Bravo AF: 0.297

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs836177; hg19: chr12-50491821;