chr6-29792650-A-C

Position:

• chr6-29792650-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NR_002139.2(HCG4):​n.424T>G variant causes a non coding transcript exon 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HCG4 NR_002139.2 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.141

Genes affected

HCG4 (HGNC:21241): (HLA complex group 4)

HLA-V (HGNC:23482): (major histocompatibility complex, class I, V (pseudogene))

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCG4	NR_002139.2	n.424T>G		non_coding_transcript_exon_variant	1/1
HLA-V	NR_132323.1	n.614A>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCG4	ENST00000418983.1	n.101T>G		non_coding_transcript_exon_variant	1/1
HLA-V	ENST00000429037.2	n.286A>C		non_coding_transcript_exon_variant	2/3
HLA-V	ENST00000476601.5	n.614A>C		non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.512A>C (p.Q171P) alteration is located in exon 2 (coding exon 2) of the LOC554223 gene. This alteration results from a A to C substitution at nucleotide position 512, causing the glutamine (Q) at amino acid position 171 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.6
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs751493222; hg19: chr6-29760427;