6-29728077-G-C

Variant names:

• chr6-29728077-G-C
• rs2735059
• XM_017010810.1:c.1279G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000957138.1(HLA-F):​c.*902G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: HLA-F ENST00000957138.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 30 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000957138.1. 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-AS1	NR_026972.1		n.1366+288C>G		intron	N/A
	HLA-F-AS1	NR_026973.1		n.151-938C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F	ENST00000957138.1		c.*902G>C		3_prime_UTR	Exon 8 of 8	ENSP00000627197.1
	HLA-F	ENST00000899563.1		c.*902G>C		3_prime_UTR	Exon 6 of 6	ENSP00000569622.1
	HLA-F	ENST00000475996.1	TSL:6	c.*14G>C		3_prime_UTR	Exon 2 of 2	ENSP00000486309.1	A0A0D9SF55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs2735059; hg19: chr6-29695854;