18-2733992-C-T

Variant summary

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

The NM_015295.3(SMCHD1):c.3276+1500C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,014 control chromosomes in the GnomAD database, including 26,196 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 0.58 (26196 hom., cov: 31)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCHD1	NM_015295.3	c.3276+1500C>T		intron_variant		ENST00000320876.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCHD1	ENST00000320876.11	c.3276+1500C>T		intron_variant		5	NM_015295.3	P2
	ENST00000583546.1	n.371-42112G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88426 AN: 151896 Hom.: 26166 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.582 AC: 88512 AN: 152014 Hom.: 26196 Cov.: 31 AF XY: 0.584 AC XY: 43414 AN XY: 74314

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.605

Alfa AF: 0.555 Hom.: 43061

Bravo AF: 0.593

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.7
Dann	Benign	0.53

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: rs1893123; hg19: chr18-2733990;