Genetic Variant NM_001123366.2:c.72+5G>A (chr18-63953532-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001123366.2(HMSD):c.72+5G>A variant causes a splice region, 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. 2/3 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_region, intron

Scores

Splicing: ADA: 0.06458

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Publications

25 publications found

Variant links:

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]

HMSD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HMSD	NM_001123366.2 link	c.72+5G>A	splice_region_variant, intron_variant	Intron 2 of 3	ENST00000408945.5	NP_001116838.1	A8MTL9-1
HMSD	XM_017025710.2 link	c.72+5G>A	splice_region_variant, intron_variant	Intron 2 of 4		XP_016881199.1
HMSD	XM_011525930.3 link	c.72+5G>A	splice_region_variant, intron_variant	Intron 2 of 4		XP_011524232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMSD	ENST00000408945.5 link	c.72+5G>A		splice_region_variant, intron_variant	Intron 2 of 3	3	NM_001123366.2	ENSP00000386207.3		A8MTL9-1
HMSD	ENST00000481726.1 link	n.45-876G>A		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40691

AN:

151994

Hom.:

6012

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.238

AC:

59070

AN:

248608

AF XY:

0.228

show subpopulations

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 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.:

AF XY:

0.213

AC XY:

154198

AN XY:

724852

show subpopulations

African (AFR)

AF:

0.400

AC:

13316

AN:

33312

American (AMR)

AF:

0.355

AC:

15851

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3902

AN:

26108

East Asian (EAS)

AF:

0.176

AC:

6977

AN:

39644

South Asian (SAS)

AF:

0.194

AC:

16740

AN:

86136

European-Finnish (FIN)

AF:

0.186

AC:

9925

AN:

53358

Middle Eastern (MID)

AF:

0.248

AC:

1425

AN:

5750

European-Non Finnish (NFE)

AF:

0.208

AC:

230043

AN:

1107330

Other (OTH)

AF:

0.229

AC:

13777

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

10620

21240

31861

42481

53101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.268

AC:

40750

AN:

152112

Hom.:

6027

Cov.:

AF XY:

0.267

AC XY:

19876

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.389

AC:

16121

AN:

41478

American (AMR)

AF:

0.326

AC:

4983

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3470

East Asian (EAS)

AF:

0.231

AC:

1199

AN:

5180

South Asian (SAS)

AF:

0.207

AC:

996

AN:

4822

European-Finnish (FIN)

AF:

0.190

AC:

2012

AN:

10578

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14112

AN:

67990

Other (OTH)

AF:

0.272

AC:

574

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1490

2980

4470

5960

7450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.240

Hom.:

3816

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

(source)

DANN

Benign

0.41

PhyloP100

-2.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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NM_001123366.2:c.72+5G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over