rs10502304

chr18-2728688-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015295.3(SMCHD1):c.2913+92T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,322,634 control chromosomes in the GnomAD database, including 33,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3113 hom., cov: 32)
  • Exomes 𝑓: 0.22 (30149 hom.)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 18-2728688-T-A is Benign according to our data. Variant chr18-2728688-T-A is described in ClinVar as [Benign]. Clinvar id is 1266007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMCHD1	NM_015295.3	c.2913+92T>A		intron_variant		ENST00000320876.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMCHD1	ENST00000320876.11	c.2913+92T>A		intron_variant		5	NM_015295.3	P2
	ENST00000583546.1	n.371-36808A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29465 AN: 151878 Hom.: 3105 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.221 AC: 259259 AN: 1170638 Hom.: 30149 Cov.: 15 AF XY: 0.223 AC XY: 129588 AN XY: 581820

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.0754

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.194 AC: 29486 AN: 151996 Hom.: 3113 Cov.: 32 AF XY: 0.196 AC XY: 14567 AN XY: 74288

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0763

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.202

Alfa AF: 0.211 Hom.: 441

Bravo AF: 0.193

Asia WGS AF: 0.200 AC: 697 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	4.4
Dann	Benign	0.66

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: rs10502304; hg19: chr18-2728686; COSMIC: COSV55253334; COSMIC: COSV55253334;