rs17875380

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001098479.2(HLA-F):c.212C>A(p.Pro71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,606,318 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0095 ( 15 hom., cov: 34)

Exomes 𝑓: 0.012 ( 141 hom. )

Consequence

HLA-F
NM_001098479.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.740

Publications

16 publications found

Variant links:

Genes affected

HLA-F (HGNC:4963): (major histocompatibility complex, class I, F) This gene belongs to the HLA class I heavy chain paralogues. It encodes a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in some cell types. It contains a divergent peptide-binding groove, and is thought to bind a restricted subset of peptides for immune presentation. This gene exhibits few polymorphisms. Multiple transcript variants encoding different isoforms have been found for this gene. These variants lack a coding exon found in transcripts from other HLA paralogues due to an altered splice acceptor site, resulting in a shorter cytoplasmic domain. [provided by RefSeq, Jul 2008]

HLA-F links:

ENSG00000225864 (HGNC:):

ENSG00000225864 links:

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

HLA-F-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 (MetaRNN=0.016821384).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00952 (1451/152344) while in subpopulation NFE AF = 0.0162 (1100/68032). AF 95% confidence interval is 0.0154. There are 15 homozygotes in GnomAd4. There are 677 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098479.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HLA-F	NM_001098479.2	MANE Select	c.212C>A	p.Pro71Gln	missense	Exon 2 of 7	NP_001091949.1
HLA-F	NM_018950.3		c.212C>A	p.Pro71Gln	missense	Exon 2 of 7	NP_061823.2
HLA-F	NM_001098478.2		c.212C>A	p.Pro71Gln	missense	Exon 2 of 6	NP_001091948.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HLA-F	ENST00000259951.12	TSL:6 MANE Select	c.212C>A	p.Pro71Gln	missense	Exon 2 of 7	ENSP00000259951.6
HLA-F	ENST00000334668.8	TSL:6	c.212C>A	p.Pro71Gln	missense	Exon 2 of 7	ENSP00000334263.4
HLA-F	ENST00000376861.5	TSL:6	c.212C>A	p.Pro71Gln	missense	Exon 3 of 8	ENSP00000366057.1

Frequencies

GnomAD3 genomes

AF:

0.00953

AC:

1451

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.0102

AC:

2346

AN:

229750

AF XY:

0.0106

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.0000594

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.0164

Gnomad OTH exome

AF:

0.00787

GnomAD4 exome

AF:

0.0121

AC:

17550

AN:

1453974

Hom.:

141

Cov.:

AF XY:

0.0118

AC XY:

8530

AN XY:

722774

show subpopulations

African (AFR)

AF:

0.00174

AC:

AN:

33262

American (AMR)

AF:

0.00212

AC:

AN:

43776

Ashkenazi Jewish (ASJ)

AF:

0.000886

AC:

AN:

25956

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39270

South Asian (SAS)

AF:

0.00859

AC:

733

AN:

85354

European-Finnish (FIN)

AF:

0.0112

AC:

579

AN:

51756

Middle Eastern (MID)

AF:

0.00789

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0140

AC:

15575

AN:

1108788

Other (OTH)

AF:

0.00735

AC:

442

AN:

60110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1104

2208

3313

4417

5521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00952

AC:

1451

AN:

152344

Hom.:

Cov.:

AF XY:

0.00909

AC XY:

677

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00303

AC:

126

AN:

41582

American (AMR)

AF:

0.00209

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0108

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0113

AC:

120

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1100

AN:

68032

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

161

242

322

403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0128

Hom.:

Bravo

AF:

0.00800

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0169

AC:

ESP6500AA

AF:

0.00365

AC:

ESP6500EA

AF:

0.0128

AC:

ExAC

AF:

0.0108

AC:

1299

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.3

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.16

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.22

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

PhyloP100

-0.74

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.15

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.028

Polyphen

0.0060

Vest4

0.038

MPC

0.73

ClinPred

0.085

GERP RS

1.6

PromoterAI

0.050

Neutral

(source)

Varity_R

0.17

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over