Variant rs3213926 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015295.3(SMCHD1):c.5476+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,465,200 control chromosomes in the GnomAD database, including 69,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6737 hom., cov: 33)

Exomes 𝑓: 0.30 ( 62728 hom. )

Consequence

SMCHD1
NM_015295.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.337

Variant links:

Genes affected

SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]

SMCHD1 links:

SMCHD1 (HGNC:):

SMCHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 18-2777925-A-G is Benign according to our data. Variant chr18-2777925-A-G is described in ClinVar as [Benign]. Clinvar id is 260654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2777925-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCHD1	NM_015295.3 linkuse as main transcript	c.5476+10A>G		intron_variant		ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11 linkuse as main transcript	c.5476+10A>G		intron_variant		5	NM_015295.3	ENSP00000326603.7		A6NHR9-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44402

AN:

151986

Hom.:

6725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.344

AC:

48452

AN:

140654

Hom.:

8957

AF XY:

0.346

AC XY:

25579

AN XY:

74014

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.525

Gnomad SAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.303

AC:

397439

AN:

1313096

Hom.:

62728

Cov.:

AF XY:

0.305

AC XY:

198031

AN XY:

648844

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.292

AC:

44442

AN:

152104

Hom.:

6737

Cov.:

AF XY:

0.294

AC XY:

21851

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.265

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.286

Hom.:

2073

Bravo

AF:

0.302

Asia WGS

AF:

0.487

AC:

1689

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Mar 24, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Facioscapulohumeral muscular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Arrhinia with choanal atresia and microphthalmia syndrome

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

-0.82

CADD

Benign

7.8

DANN

Benign

0.33

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

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