18-63966010-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMSD	XM_017025710.2	c.341-2328T>C		intron_variant	Intron 4 of 4		XP_016881199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMSD	ENST00000481726.1	n.312+5735T>C		intron_variant	Intron 3 of 5	5
HMSD	ENST00000498680.1	n.95-2328T>C		intron_variant	Intron 1 of 1	5

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

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.293

Alfa AF: 0.231 Hom.: 4287

Bravo AF: 0.314

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2009989; hg19: chr18-61633244;