Genetic Variant ENST00000425174.1:n.-238A>C (chr6-31382526-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000425174.1(HLA-S):n.-238A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,958 control chromosomes in the GnomAD database, including 6,239 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 0.28 ( 6239 hom., cov: 31)

Consequence

HLA-S
ENST00000425174.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.289

Publications

12 publications found

Variant links:

Genes affected

HLA-S (HGNC:19395): (major histocompatibility complex, class I, S (pseudogene))

HLA-S links:

MICA-AS1 (HGNC:):

MICA-AS1 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
HLA-S	ENST00000425174.1 link	n.-238A>C	upstream_gene_variant	6
MICA-AS1	ENST00000745027.1 link	n.*185A>C	downstream_gene_variant
MICA-AS1	ENST00000745028.1 link	n.*216A>C	downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43060

AN:

151840

Hom.:

6228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.266

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

GnomAD4 genome

AF:

0.284

AC:

43117

AN:

151958

Hom.:

6239

Cov.:

AF XY:

0.284

AC XY:

21072

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.337

AC:

13958

AN:

41382

American (AMR)

AF:

0.257

AC:

3926

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

952

AN:

3468

East Asian (EAS)

AF:

0.202

AC:

1040

AN:

5156

South Asian (SAS)

AF:

0.311

AC:

1498

AN:

4824

European-Finnish (FIN)

AF:

0.273

AC:

2882

AN:

10576

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.261

AC:

17768

AN:

67968

Other (OTH)

AF:

0.270

AC:

569

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1556

3113

4669

6226

7782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.162

Hom.:

340

Bravo

AF:

0.281

Asia WGS

AF:

0.239

AC:

831

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.0

(source)

DANN

Benign

0.54

PhyloP100

-0.29

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over