chr6-29736306-C-T

Position:

• chr6-29736306-C-T

Variant summary

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

The XM_017010813.2(HLA-F):​c.1159-1816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 399,080 control chromosomes in the GnomAD database, including 140,767 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 0.82 (51072 hom., cov: 32)
  • Exomes 𝑓: 0.85 (89695 hom.)
• Consequence: HLA-F XM_017010813.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-F	XM_017010813.2	c.1159-1816C>T		intron_variant			XP_016866302.1
HLA-F	XM_011514564.2	c.1004-1816C>T		intron_variant			XP_011512866.1
HLA-F	XM_047418720.1	c.1004-1816C>T		intron_variant			XP_047274676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-F	ENST00000465459.2	c.404-1816C>T		intron_variant		6		ENSP00000486947.1
HLA-F-AS1	ENST00000458236.1	n.1557G>A		non_coding_transcript_exon_variant	6/6	6
HLA-F-AS1	ENST00000399247.6	n.1235+1660G>A		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124165 AN: 152040 Hom.: 51011 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.850 AC: 209789 AN: 246920 Hom.: 89695 Cov.: 0 AF XY: 0.858 AC XY: 121343 AN XY: 141392

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.902

Gnomad4 ASJ exome AF: 0.883

Gnomad4 EAS exome AF: 0.987

Gnomad4 SAS exome AF: 0.918

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.830

GnomAD4 genome AF: 0.817 AC: 124286 AN: 152160 Hom.: 51072 Cov.: 32 AF XY: 0.815 AC XY: 60609 AN XY: 74376

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.825

Alfa AF: 0.831 Hom.: 19755

Bravo AF: 0.828

Asia WGS AF: 0.939 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1736916; hg19: chr6-29704083;