rs8092725

Variant names:

• chr18-2738261-G-A
• rs8092725
• NM_015295.3:c.3277-136G>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.3277-136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 724,526 control chromosomes in the GnomAD database, including 17,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3115 hom., cov: 32)
  • Exomes 𝑓: 0.22 (14627 hom.)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ENSG00000266049 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 18-2738261-G-A is Benign according to our data. Variant chr18-2738261-G-A is described in ClinVar as [Benign]. Clinvar id is 1224606.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 rank	MANE	Protein	UniProt
SMCHD1	NM_015295.3	c.3277-136G>A		intron_variant	Intron 25 of 47	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11	c.3277-136G>A		intron_variant	Intron 25 of 47	5	NM_015295.3	ENSP00000326603.7

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29503 AN: 151922 Hom.: 3107 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.220 AC: 125788 AN: 572486 Hom.: 14627 AF XY: 0.221 AC XY: 64711 AN XY: 292984

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0753

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.194 AC: 29524 AN: 152040 Hom.: 3115 Cov.: 32 AF XY: 0.196 AC XY: 14590 AN XY: 74310

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.0772

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.203

Alfa AF: 0.219 Hom.: 5075

Bravo AF: 0.193

Asia WGS AF: 0.199 AC: 694 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.2
DANN	Benign	0.65

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: rs8092725; hg19: chr18-2738259;