rs574972

Variant names:

• chr18-2686851-A-G
• rs574972
• NM_015295.3:c.639-1543A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-2686851-A-G
• chr18-2686851-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015295.3(SMCHD1):​c.639-1543A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,098 control chromosomes in the GnomAD database, including 55,088 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (55088 hom., cov: 31)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCHD1	NM_015295.3	c.639-1543A>G		intron_variant	Intron 5 of 47	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11	c.639-1543A>G		intron_variant	Intron 5 of 47	5	NM_015295.3	ENSP00000326603.7
SMCHD1	ENST00000688342.1	c.639-1543A>G		intron_variant	Intron 5 of 46			ENSP00000508422.1
SMCHD1	ENST00000684915.1	n.796-1543A>G		intron_variant	Intron 5 of 13

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125289 AN: 151980 Hom.: 55071 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.839

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.824 AC: 125337 AN: 152098 Hom.: 55088 Cov.: 31 AF XY: 0.828 AC XY: 61604 AN XY: 74380

African (AFR) AF: 0.483 AC: 20019 AN: 41412

American (AMR) AF: 0.903 AC: 13812 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3230 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5178 AN: 5186

South Asian (SAS) AF: 0.969 AC: 4680 AN: 4830

European-Finnish (FIN) AF: 0.974 AC: 10336 AN: 10608

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.959 AC: 65176 AN: 67990

Other (OTH) AF: 0.841 AC: 1771 AN: 2106

Alfa AF: 0.794 Hom.: 3648

Bravo AF: 0.804

Asia WGS AF: 0.957 AC: 3328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.74
PhyloP100		-0.27
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

Other links and lift over

dbSNP: rs574972; hg19: chr18-2686849;