rs10853283

chr18-2715729-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015295.3(SMCHD1):c.2261-2429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,016 control chromosomes in the GnomAD database, including 6,839 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 0.29 (6839 hom., cov: 31)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCHD1	NM_015295.3	c.2261-2429T>C		intron_variant		ENST00000320876.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCHD1	ENST00000320876.11	c.2261-2429T>C		intron_variant		5	NM_015295.3	P2
	ENST00000583546.1	n.371-23849A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44728 AN: 151898 Hom.: 6823 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.295 AC: 44776 AN: 152016 Hom.: 6839 Cov.: 31 AF XY: 0.297 AC XY: 22050 AN XY: 74300

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.302

Alfa AF: 0.288 Hom.: 802

Bravo AF: 0.304

Asia WGS AF: 0.491 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.87
Dann	Benign	0.26

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

Other links and lift over

dbSNP: rs10853283; hg19: chr18-2715727;