rs10502307

Positions:

• chr18-2800827-G-A

Variant summary

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

The NM_015295.3(SMCHD1):​c.5994-1701G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,122 control chromosomes in the GnomAD database, including 2,789 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 0.18 (2789 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCHD1	NM_015295.3	c.5994-1701G>A		intron_variant		ENST00000320876.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCHD1	ENST00000320876.11	c.5994-1701G>A		intron_variant		5	NM_015295.3	P2
	ENST00000583546.1	n.370+7628C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27818 AN: 152004 Hom.: 2781 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.180

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.183 AC: 27843 AN: 152122 Hom.: 2789 Cov.: 32 AF XY: 0.184 AC XY: 13654 AN XY: 74372

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0250

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.181

Alfa AF: 0.203 Hom.: 408

Bravo AF: 0.183

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.17
DANN	Benign	0.31

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: rs10502307; hg19: chr18-2800825;