Variant 18-2705814-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015295.3(SMCHD1):c.1956+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,489,544 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 12 hom. )

Consequence

SMCHD1
NM_015295.3 splice_region, intron

Scores

Splicing: ADA: 0.0001359

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.566

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 18-2705814-C-T is Benign according to our data. Variant chr18-2705814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2705814-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00198 (301/152118) while in subpopulation AMR AF= 0.00386 (59/15284). AF 95% confidence interval is 0.00307. There are 0 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMCHD1	NM_015295.3 linkuse as main transcript	c.1956+7C>T		splice_region_variant, intron_variant		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.1956+7C>T		splice_region_variant, intron_variant		5	NM_015295.3	ENSP00000326603.7		A6NHR9-1

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.000568

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00299

Gnomad OTH

AF:

0.00672

GnomAD3 exomes

AF:

0.00237

AC:

569

AN:

239758

Hom.:

AF XY:

0.00237

AC XY:

309

AN XY:

130150

show subpopulations

Gnomad AFR exome

AF:

0.000330

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.000205

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000704

Gnomad FIN exome

AF:

0.00108

Gnomad NFE exome

AF:

0.00386

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00232

AC:

3100

AN:

1337426

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

1591

AN XY:

671490

show subpopulations

Gnomad4 AFR exome

AF:

0.000679

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.000160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000806

Gnomad4 FIN exome

AF:

0.00143

Gnomad4 NFE exome

AF:

0.00259

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152118

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000568

Gnomad4 NFE

AF:

0.00299

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 30, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 21, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	SMCHD1: BP4, BS1 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Facioscapulohumeral muscular dystrophy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.3

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0040

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