rs7139363

Positions:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000394963.9(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 ENST00000394963.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.47

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD1	NM_003076.5	c.1269+192G>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.1269+192G>A		intron_variant		1	NM_003076.5	ENSP00000378414	P1
SMARCD1	ENST00000381513.8	c.1269+192G>A		intron_variant		1		ENSP00000370924
SMARCD1	ENST00000548573.5	c.663+192G>A		intron_variant		5		ENSP00000448627
SMARCD1	ENST00000549274.1	c.67+192G>A		intron_variant, NMD_transcript_variant		3		ENSP00000447909

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

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.270

Alfa AF: 0.228 Hom.: 3956

Bravo AF: 0.254

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.055
DANN	Benign	0.67

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: rs7139363; hg19: chr12-50488547;