chr18-2705702-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015295.3(SMCHD1):c.1851A>G(p.Thr617Thr) 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:5

Conservation

PhyloP100: 0.334

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

arhinia, choanal atresia, and microphthalmia
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, ClinGen, Illumina
facioscapulohumeral muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SMCHD1 links:

ENSG00000266049 (HGNC:):

ENSG00000266049 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 260633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SMCHD1	NM_015295.3 link	c.1851A>G	p.Thr617Thr	synonymous_variant	Exon 14 of 48	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11 link	c.1851A>G	p.Thr617Thr	synonymous_variant	Exon 14 of 48	5	NM_015295.3	ENSP00000326603.7		A6NHR9-1

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

GnomAD2 exomes

AF:

0.694

AC:

167030

AN:

240620

AF XY:

0.695

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 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

African (AFR)

AF:

0.309

AC:

10044

AN:

32500

American (AMR)

AF:

0.768

AC:

33229

AN:

43270

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

16274

AN:

25334

East Asian (EAS)

AF:

0.674

AC:

26276

AN:

38980

South Asian (SAS)

AF:

0.649

AC:

53146

AN:

81898

European-Finnish (FIN)

AF:

0.751

AC:

39101

AN:

52040

Middle Eastern (MID)

AF:

0.565

AC:

3159

AN:

5590

European-Non Finnish (NFE)

AF:

0.730

AC:

775637

AN:

1062116

Other (OTH)

AF:

0.681

AC:

39494

AN:

57996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

10949

21897

32846

43794

54743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18912

37824

56736

75648

94560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.612

AC:

92474

AN:

151094

Hom.:

30718

Cov.:

AF XY:

0.615

AC XY:

45350

AN XY:

73798

show subpopulations

African (AFR)

AF:

0.331

AC:

13644

AN:

41256

American (AMR)

AF:

0.718

AC:

10883

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

2278

AN:

3470

East Asian (EAS)

AF:

0.680

AC:

3506

AN:

5154

South Asian (SAS)

AF:

0.644

AC:

3092

AN:

4802

European-Finnish (FIN)

AF:

0.753

AC:

7674

AN:

10196

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.728

AC:

49353

AN:

67756

Other (OTH)

AF:

0.612

AC:

1280

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1508

3017

4525

6034

7542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.683

Hom.:

86533

Bravo

AF:

0.599

Asia WGS

AF:

0.663

AC:

2301

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 24, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Facioscapulohumeral muscular dystrophy 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arrhinia with choanal atresia and microphthalmia syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.6

(source)

DANN

Benign

0.70

PhyloP100

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over