18-2740800-A-T

Variant names:

• chr18-2740800-A-T
• rs115632137
• NM_015295.3:c.3612A>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015295.3(SMCHD1):​c.3612A>T​(p.Ser1204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,605,366 control chromosomes in the GnomAD database, including 471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (244 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (227 hom.)
• Consequence: SMCHD1 NM_015295.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0650

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]

ENSG00000266049 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 18-2740800-A-T is Benign according to our data. Variant chr18-2740800-A-T is described in ClinVar as [Benign]. Clinvar id is 260644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2740800-A-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.065 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCHD1	NM_015295.3	c.3612A>T	p.Ser1204Ser	synonymous_variant	Exon 28 of 48	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11	c.3612A>T	p.Ser1204Ser	synonymous_variant	Exon 28 of 48	5	NM_015295.3	ENSP00000326603.7

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 4736 AN: 152154 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00776 AC: 1911 AN: 246208 AF XY: 0.00599

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00442

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000463

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00321 AC: 4662 AN: 1453094 Hom.: 227 Cov.: 29 AF XY: 0.00277 AC XY: 2002 AN XY: 723040

African (AFR) AF: 0.112 AC: 3716 AN: 33196

American (AMR) AF: 0.00518 AC: 229 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.000306 AC: 26 AN: 85004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00575 AC: 33 AN: 5742

European-Non Finnish (NFE) AF: 0.000219 AC: 242 AN: 1106340

Other (OTH) AF: 0.00693 AC: 416 AN: 60010

GnomAD4 genome AF: 0.0311 AC: 4743 AN: 152272 Hom.: 244 Cov.: 32 AF XY: 0.0304 AC XY: 2267 AN XY: 74456

African (AFR) AF: 0.108 AC: 4467 AN: 41540

American (AMR) AF: 0.0118 AC: 181 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68014

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.00188 Hom.: 4

Bravo AF: 0.0353

Asia WGS AF: 0.00405 AC: 14 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 16, 2023

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Apr 15, 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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		-0.065
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs115632137; hg19: chr18-2740798;