Variant rs635132 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015295.3(SMCHD1):c.1851A>G(p.Thr617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,550,818 control chromosomes in the GnomAD database, including 389,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30718 hom., cov: 28)

Exomes 𝑓: 0.71 ( 359182 hom. )

Consequence

SMCHD1
NM_015295.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.334

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 18-2705702-A-G is Benign according to our data. Variant chr18-2705702-A-G is described in ClinVar as [Benign]. Clinvar id is 260633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2705702-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.334 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCHD1	NM_015295.3 linkuse as main transcript	c.1851A>G	p.Thr617=	synonymous_variant	14/48	ENST00000320876.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCHD1	ENST00000320876.11 linkuse as main transcript	c.1851A>G	p.Thr617=	synonymous_variant	14/48	5	NM_015295.3	P2	A6NHR9-1
	ENST00000583546.1 linkuse as main transcript	n.371-13822T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92435

AN:

150978

Hom.:

30704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.672

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.753

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.610

GnomAD3 exomes

AF:

0.694

AC:

167030

AN:

240620

Hom.:

59460

AF XY:

0.695

AC XY:

90941

AN XY:

130864

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.653

Gnomad EAS exome

AF:

0.673

Gnomad SAS exome

AF:

0.652

Gnomad FIN exome

AF:

0.758

Gnomad NFE exome

AF:

0.726

Gnomad OTH exome

AF:

0.694

GnomAD4 exome

AF:

0.712

AC:

996360

AN:

1399724

Hom.:

359182

Cov.:

AF XY:

0.710

AC XY:

496261

AN XY:

699028

show subpopulations

Gnomad4 AFR exome

AF:

0.309

Gnomad4 AMR exome

AF:

0.768

Gnomad4 ASJ exome

AF:

0.642

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.649

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.730

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.612

AC:

92474

AN:

151094

Hom.:

30718

Cov.:

AF XY:

0.615

AC XY:

45350

AN XY:

73798

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.718

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.680

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.753

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.706

Hom.:

52803

Bravo

AF:

0.599

Asia WGS

AF:

0.663

AC:

2301

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2021

- -

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

-0.51

CADD

Benign

6.6

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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