6-29725284-C-G

Variant names:

• chr6-29725284-C-G
• rs1405929879
• NM_001098479.2:c.864C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001098479.2(HLA-F):​c.864C>G​(p.Pro288Pro) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HLA-F NM_001098479.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.025).
• BP6: Variant 6-29725284-C-G is Benign according to our data. Variant chr6-29725284-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.52 with no splicing effect.

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.864C>G	p.Pro288Pro	synonymous	Exon 4 of 7	NP_001091949.1	P30511-3
	HLA-F	NM_018950.3		c.864C>G	p.Pro288Pro	synonymous	Exon 4 of 7	NP_061823.2	Q5JZ47
	HLA-F	NM_001098478.2		c.611-163C>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.864C>G	p.Pro288Pro	synonymous	Exon 4 of 7	ENSP00000259951.6	P30511-3
	HLA-F	ENST00000957138.1		c.864C>G	p.Pro288Pro	synonymous	Exon 5 of 8	ENSP00000627197.1
	HLA-F	ENST00000899563.1		c.864C>G	p.Pro288Pro	synonymous	Exon 4 of 6	ENSP00000569622.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.63
DANN	Benign	0.54
PhyloP100		-2.5
PromoterAI		-0.0039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1405929879; hg19: chr6-29693061;