rs9945924

chr18-63953532-G-Achr18-63953532-G-C

Variant summary

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

The NM_001123366.2(HMSD):c.72+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,608,586 control chromosomes in the GnomAD database, including 41,168 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6027 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35141 hom.)
• Consequence: HMSD NM_001123366.2 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.06458
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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 = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMSD	NM_001123366.2	c.72+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000408945.5
HMSD	XM_011525930.3	c.72+5G>A		splice_donor_5th_base_variant, intron_variant
HMSD	XM_017025710.2	c.72+5G>A		splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMSD	ENST00000408945.5	c.72+5G>A		splice_donor_5th_base_variant, intron_variant		3	NM_001123366.2	P1
HMSD	ENST00000481726.1	n.45-876G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40691 AN: 151994 Hom.: 6012 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.272

GnomAD3 exomes AF: 0.238 AC: 59070 AN: 248608 Hom.: 7746 AF XY: 0.228 AC XY: 30865 AN XY: 135078

Gnomad AFR exome AF: 0.395

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.214 AC: 311956 AN: 1456474 Hom.: 35141 Cov.: 29 AF XY: 0.213 AC XY: 154198 AN XY: 724852

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.268 AC: 40750 AN: 152112 Hom.: 6027 Cov.: 33 AF XY: 0.267 AC XY: 19876 AN XY: 74370

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.272

Alfa AF: 0.230 Hom.: 2032

Bravo AF: 0.284

Asia WGS AF: 0.239 AC: 833 AN: 3478

EpiCase AF: 0.221

EpiControl AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0030
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.065
dbscSNV1_RF	Benign	0.076
SpliceAI score (max)		0.60		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.60		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs9945924; hg19: chr18-61620766; COSMIC: COSV68816842; COSMIC: COSV68816842;