Variant 6-29723805-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-F	NM_001098479.2 link	c.212C>A	p.Pro71Gln	missense_variant	2/7	ENST00000259951.12	NP_001091949.1	P30511-3Q5JZ48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000259951.12 link	c.212C>A	p.Pro71Gln	missense_variant	2/7	6	NM_001098479.2	ENSP00000259951.6		P30511-3

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

GnomAD3 exomes

AF:

0.0102

AC:

2346

AN:

229750

Hom.:

AF XY:

0.0106

AC XY:

1327

AN XY:

125650

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 SAS exome

AF:

0.00914

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

Gnomad4 AFR exome

AF:

0.00174

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.000886

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.00859

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.00735

GnomAD4 genome

AF:

0.00952

AC:

1451

AN:

152344

Hom.:

Cov.:

AF XY:

0.00909

AC XY:

677

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00303

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.0131

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.3

DANN

Benign

0.94

DEOGEN2

Benign

0.16

T;.;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.22

.;T;T;T

MetaRNN

Benign

0.017

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;M;M;M

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.5

D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.028

D;D;D;D

Polyphen

0.0060

B;B;B;B

Vest4

0.038

MPC

0.73

ClinPred

0.085

GERP RS

1.6

Varity_R

0.17

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over