Variant rs2304859 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.4137A>G(p.Ala1379Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,603,420 control chromosomes in the GnomAD database, including 78,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6924 hom., cov: 31)

Exomes 𝑓: 0.31 ( 71276 hom. )

Consequence

SMCHD1
NM_015295.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.324

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 18-2750479-A-G is Benign according to our data. Variant chr18-2750479-A-G is described in ClinVar as [Benign]. Clinvar id is 260648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2750479-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.324 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 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.4137A>G	p.Ala1379Ala	synonymous_variant	32/48	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.4137A>G	p.Ala1379Ala	synonymous_variant	32/48	5	NM_015295.3	ENSP00000326603.7		A6NHR9-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45156

AN:

151810

Hom.:

6908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.345

AC:

82065

AN:

237782

Hom.:

15227

AF XY:

0.343

AC XY:

44174

AN XY:

128892

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.505

Gnomad SAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.306

AC:

444643

AN:

1451492

Hom.:

71276

Cov.:

AF XY:

0.309

AC XY:

223004

AN XY:

721618

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.467

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.298

AC:

45204

AN:

151928

Hom.:

6924

Cov.:

AF XY:

0.300

AC XY:

22262

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.292

Hom.:

8661

Bravo

AF:

0.307

Asia WGS

AF:

0.491

AC:

1709

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 02, 2018	- -

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

-0.60

CADD

Benign

4.5

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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