Variant 18-2763699-C-T 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.4629C>T(p.Gly1543=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,605,584 control chromosomes in the GnomAD database, including 142,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11751 hom., cov: 32)

Exomes 𝑓: 0.42 ( 130630 hom. )

Consequence

SMCHD1
NM_015295.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.850

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=-0.57).

BP6

Variant 18-2763699-C-T is Benign according to our data. Variant chr18-2763699-C-T is described in ClinVar as [Benign]. Clinvar id is 260650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2763699-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 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.4629C>T	p.Gly1543=	synonymous_variant	37/48	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.4629C>T	p.Gly1543=	synonymous_variant	37/48	5	NM_015295.3	ENSP00000326603	P2	A6NHR9-1
	ENST00000583546.1 linkuse as main transcript	n.370+44756G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58294

AN:

151866

Hom.:

11749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.366

GnomAD3 exomes

AF:

0.361

AC:

87017

AN:

241252

Hom.:

17336

AF XY:

0.360

AC XY:

47238

AN XY:

131240

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.444

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.415

AC:

603963

AN:

1453600

Hom.:

130630

Cov.:

AF XY:

0.409

AC XY:

296003

AN XY:

723192

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.384

AC:

58317

AN:

151984

Hom.:

11751

Cov.:

AF XY:

0.381

AC XY:

28325

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.476

Gnomad4 NFE

AF:

0.451

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.391

Hom.:

6226

Bravo

AF:

0.370

Asia WGS

AF:

0.179

AC:

624

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 06, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.2

DANN

Benign

0.73

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