6-29737882-A-G

Position:

• chr6-29737882-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017010813.2(HLA-F):​c.1159-240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,062 control chromosomes in the GnomAD database, including 12,015 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 0.39 (12007 hom., cov: 31)
  • Exomes 𝑓: 0.53 (8 hom.)
• Consequence: HLA-F XM_017010813.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-F	XM_017010813.2	c.1159-240A>G		intron_variant			XP_016866302.1
HLA-F	XM_011514564.2	c.1004-240A>G		intron_variant			XP_011512866.1
HLA-F	XM_047418720.1	c.1004-240A>G		intron_variant			XP_047274676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000465459.2	c.404-240A>G		intron_variant		6		ENSP00000486947.1
HLA-F-AS1	ENST00000434086.1	n.430T>C		non_coding_transcript_exon_variant	2/2	6
HLA-F-AS1	ENST00000399247.6	n.1235+84T>C		intron_variant		6
HLA-F-AS1	ENST00000458236.1	n.1042+84T>C		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59885 AN: 151884 Hom.: 11988 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.534 AC: 31 AN: 58 Hom.: 8 Cov.: 0 AF XY: 0.500 AC XY: 24 AN XY: 48

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.394 AC: 59941 AN: 152004 Hom.: 12007 Cov.: 31 AF XY: 0.394 AC XY: 29266 AN XY: 74300

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.395

Alfa AF: 0.424 Hom.: 17675

Bravo AF: 0.393

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.7
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523393; hg19: chr6-29705659;