Variant 12-50086152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000394963.9(SMARCD1):c.178-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,530,350 control chromosomes in the GnomAD database, including 871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 256 hom., cov: 31)

Exomes 𝑓: 0.012 ( 615 hom. )

Consequence

SMARCD1
ENST00000394963.9 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001052

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.171

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 12-50086152-C-T is Benign according to our data. Variant chr12-50086152-C-T is described in ClinVar as [Benign]. Clinvar id is 1283034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD1	NM_003076.5 linkuse as main transcript	c.178-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000394963.9	NP_003067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9 linkuse as main transcript	c.178-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003076.5	ENSP00000378414	P1	Q96GM5-1

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5681

AN:

152078

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0635

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.0548

Gnomad SAS

AF:

0.0460

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.0355

GnomAD3 exomes

AF:

0.0330

AC:

6506

AN:

197228

Hom.:

298

AF XY:

0.0291

AC XY:

3069

AN XY:

105572

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.00959

Gnomad EAS exome

AF:

0.0540

Gnomad SAS exome

AF:

0.0467

Gnomad FIN exome

AF:

0.000766

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.0226

GnomAD4 exome

AF:

0.0118

AC:

16313

AN:

1378154

Hom.:

615

Cov.:

AF XY:

0.0123

AC XY:

8352

AN XY:

676982

show subpopulations

Gnomad4 AFR exome

AF:

0.0956

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.00779

Gnomad4 EAS exome

AF:

0.0724

Gnomad4 SAS exome

AF:

0.0450

Gnomad4 FIN exome

AF:

0.000891

Gnomad4 NFE exome

AF:

0.00228

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0374

AC:

5689

AN:

152196

Hom.:

256

Cov.:

AF XY:

0.0381

AC XY:

2834

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0939

Gnomad4 AMR

AF:

0.0642

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.0545

Gnomad4 SAS

AF:

0.0450

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0275

Hom.:

Bravo

AF:

0.0457

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Coffin-Siris syndrome 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.9

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over