6-29724080-C-G

Variant names:

• chr6-29724080-C-G
• rs2072895
• NM_001098479.2:c.335-93C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098479.2(HLA-F):​c.335-93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,562,232 control chromosomes in the GnomAD database, including 146,011 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 0.42 (13781 hom., cov: 32)
  • Exomes 𝑓: 0.43 (132230 hom.)
• Consequence: HLA-F NM_001098479.2 intron
• Scores: Splicing: ADA: 0.00006217
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 22 publications found

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

ENSG00000225864 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F	NM_001098479.2	MANE Select	c.335-93C>G		intron	N/A	NP_001091949.1	P30511-3
	HLA-F	NM_018950.3		c.335-93C>G		intron	N/A	NP_061823.2	Q5JZ47
	HLA-F	NM_001098478.2		c.335-93C>G		intron	N/A	NP_001091948.1	P30511-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F	ENST00000259951.12	TSL:6 MANE Select	c.335-93C>G		intron	N/A	ENSP00000259951.6	P30511-3
	HLA-F	ENST00000957138.1		c.335-93C>G		intron	N/A	ENSP00000627197.1
	HLA-F	ENST00000899563.1		c.335-93C>G		intron	N/A	ENSP00000569622.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64449 AN: 151882 Hom.: 13765 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.435

GnomAD2 exomes AF: 0.421 AC: 71565 AN: 169952 AF XY: 0.415

Gnomad AFR exome AF: 0.382

Gnomad AMR exome AF: 0.420

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.426

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.458

Gnomad OTH exome AF: 0.427

GnomAD4 exome AF: 0.430 AC: 606294 AN: 1410230 Hom.: 132230 Cov.: 34 AF XY: 0.426 AC XY: 297476 AN XY: 697490

African (AFR) AF: 0.378 AC: 12202 AN: 32268

American (AMR) AF: 0.414 AC: 15299 AN: 36924

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 13137 AN: 25294

East Asian (EAS) AF: 0.411 AC: 15157 AN: 36876

South Asian (SAS) AF: 0.283 AC: 22963 AN: 81198

European-Finnish (FIN) AF: 0.445 AC: 21623 AN: 48584

Middle Eastern (MID) AF: 0.405 AC: 2199 AN: 5436

European-Non Finnish (NFE) AF: 0.441 AC: 478842 AN: 1085132

Other (OTH) AF: 0.425 AC: 24872 AN: 58518

GnomAD4 genome AF: 0.424 AC: 64498 AN: 152002 Hom.: 13781 Cov.: 32 AF XY: 0.423 AC XY: 31407 AN XY: 74306

African (AFR) AF: 0.390 AC: 16153 AN: 41470

American (AMR) AF: 0.426 AC: 6507 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1807 AN: 3472

East Asian (EAS) AF: 0.415 AC: 2130 AN: 5128

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4820

European-Finnish (FIN) AF: 0.435 AC: 4592 AN: 10558

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30470 AN: 67950

Other (OTH) AF: 0.433 AC: 912 AN: 2108

Alfa AF: 0.419 Hom.: 4113

Bravo AF: 0.425

Asia WGS AF: 0.328 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000062
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

Other links and lift over

dbSNP: rs2072895; hg19: chr6-29691857; COSMIC: COSV52576559; COSMIC: COSV52576559;