rs7139363

Variant names:

• chr12-50094764-G-A
• rs7139363
• NM_003076.5:c.1269+192G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-50094764-G-A
• chr12-50094764-G-C
• chr12-50094764-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003076.5(SMARCD1):​c.1269+192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,066 control chromosomes in the GnomAD database, including 5,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5745 hom., cov: 33)
• Consequence: SMARCD1 NM_003076.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.47
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-50094764-G-A is Benign according to our data. Variant chr12-50094764-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 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.1269+192G>A		intron	N/A	NP_003067.3
	SMARCD1	NM_139071.3		c.1269+192G>A		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.1269+192G>A		intron	N/A	ENSP00000378414.4	Q96GM5-1
	SMARCD1	ENST00000381513.8	TSL:1	c.1269+192G>A		intron	N/A	ENSP00000370924.4	Q96GM5-2
	SMARCD1	ENST00000915409.1		c.1296+192G>A		intron	N/A	ENSP00000585468.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37913 AN: 151948 Hom.: 5737 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.249 AC: 37921 AN: 152066 Hom.: 5745 Cov.: 33 AF XY: 0.259 AC XY: 19288 AN XY: 74346

African (AFR) AF: 0.175 AC: 7263 AN: 41458

American (AMR) AF: 0.343 AC: 5250 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3996 AN: 5184

South Asian (SAS) AF: 0.381 AC: 1834 AN: 4818

European-Finnish (FIN) AF: 0.260 AC: 2748 AN: 10554

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14807 AN: 67974

Other (OTH) AF: 0.270 AC: 570 AN: 2112

Alfa AF: 0.229 Hom.: 5292

Bravo AF: 0.254

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.055
DANN	Benign	0.67
PhyloP100		-3.5
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: rs7139363; hg19: chr12-50488547;