chr18-63966010-T-C

Variant names:

• chr18-63966010-T-C
• rs2009989
• XM_017025710.2:c.341-2328T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017025710.2(HMSD):​c.341-2328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,034 control chromosomes in the GnomAD database, including 7,665 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 (7665 hom., cov: 32)
• Consequence: HMSD XM_017025710.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 5 publications found

Genes affected

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000481726.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMSD	ENST00000481726.1	TSL:5	n.312+5735T>C		intron	N/A
	HMSD	ENST00000498680.1	TSL:5	n.95-2328T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44619 AN: 151916 Hom.: 7643 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.294 AC: 44693 AN: 152034 Hom.: 7665 Cov.: 32 AF XY: 0.293 AC XY: 21761 AN XY: 74322

African (AFR) AF: 0.477 AC: 19778 AN: 41426

American (AMR) AF: 0.337 AC: 5143 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1183 AN: 5174

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4816

European-Finnish (FIN) AF: 0.189 AC: 1999 AN: 10578

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14159 AN: 67966

Other (OTH) AF: 0.293 AC: 620 AN: 2116

Alfa AF: 0.243 Hom.: 6364

Bravo AF: 0.314

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2009989; hg19: chr18-61633244;