rs1362126

Positions:

• chr6-29723242-G-A
• chr6-29723242-G-T

Variant summary

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

The ENST00000427340.1(ENSG00000225864):​n.730C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 579,436 control chromosomes in the GnomAD database, including 42,614 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 0.35 (9767 hom., cov: 30)
  • Exomes 𝑓: 0.38 (32847 hom.)
• Consequence: ENST00000427340.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000427340.1	n.730C>T		non_coding_transcript_exon_variant	1/1
HLA-F	ENST00000376861.5	c.-158-64G>A		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53071 AN: 151836 Hom.: 9762 Cov.: 30

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.382 AC: 163378 AN: 427480 Hom.: 32847 Cov.: 4 AF XY: 0.373 AC XY: 84088 AN XY: 225490

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.349 AC: 53099 AN: 151956 Hom.: 9767 Cov.: 30 AF XY: 0.350 AC XY: 25978 AN XY: 74268

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.348

Alfa AF: 0.398 Hom.: 13743

Bravo AF: 0.343

Asia WGS AF: 0.264 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1362126; hg19: chr6-29691019;