12-50086502-A-G

Variant summary

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

The NM_003076.5(SMARCD1):c.366-119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (337 hom., cov: 0)
  • Exomes 𝑓: 0.019 (249 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMARCD1 NM_003076.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0590

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=-0.92).
• BP6: Variant 12-50086502-A-G is Benign according to our data. Variant chr12-50086502-A-G is described in ClinVar as [Benign]. Clinvar id is 1220623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCD1	NM_003076.5	c.366-119A>G		intron_variant		ENST00000394963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCD1	ENST00000394963.9	c.366-119A>G		intron_variant		1	NM_003076.5	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 5422 AN: 49222 Hom.: 330 Cov.: 0

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.00587

Gnomad EAS AF: 0.00166

Gnomad SAS AF: 0.000644

Gnomad FIN AF: 0.000371

Gnomad MID AF: 0.0286

Gnomad NFE AF: 0.00120

Gnomad OTH AF: 0.0920

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0188 AC: 6620 AN: 351874 Hom.: 249 Cov.: 10 AF XY: 0.0159 AC XY: 2884 AN XY: 181746

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.0293

Gnomad4 ASJ exome AF: 0.00596

Gnomad4 EAS exome AF: 0.00331

Gnomad4 SAS exome AF: 0.00284

Gnomad4 FIN exome AF: 0.00174

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.111 AC: 5453 AN: 49258 Hom.: 337 Cov.: 0 AF XY: 0.110 AC XY: 2593 AN XY: 23484

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.00587

Gnomad4 EAS AF: 0.00167

Gnomad4 SAS AF: 0.000646

Gnomad4 FIN AF: 0.000371

Gnomad4 NFE AF: 0.00120

Gnomad4 OTH AF: 0.0908

Alfa AF: 0.00956 Hom.: 30

Bravo AF: 0.0403

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 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.49

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: rs57224706; hg19: chr12-50480285; COSMIC: COSV57316841; COSMIC: COSV57316841;