6-29828375-G-C

Variant names:

• chr6-29828375-G-C
• rs1625907
• NM_001384290.1:c.343+59G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384290.1(HLA-G):​c.343+59G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,563,418 control chromosomes in the GnomAD database, including 189,454 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 0.50 (19203 hom., cov: 32)
  • Exomes 𝑓: 0.48 (170251 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 6 publications found

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.343+59G>C		intron_variant	Intron 2 of 6	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.343+59G>C		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75603 AN: 151878 Hom.: 19171 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.484 AC: 683453 AN: 1411422 Hom.: 170251 Cov.: 49 AF XY: 0.492 AC XY: 342147 AN XY: 695846

African (AFR) AF: 0.550 AC: 17873 AN: 32468

American (AMR) AF: 0.505 AC: 20516 AN: 40594

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 13162 AN: 22862

East Asian (EAS) AF: 0.661 AC: 25769 AN: 38962

South Asian (SAS) AF: 0.712 AC: 55454 AN: 77866

European-Finnish (FIN) AF: 0.345 AC: 17198 AN: 49802

Middle Eastern (MID) AF: 0.569 AC: 3110 AN: 5470

European-Non Finnish (NFE) AF: 0.461 AC: 500105 AN: 1085190

Other (OTH) AF: 0.520 AC: 30266 AN: 58208

GnomAD4 genome AF: 0.498 AC: 75681 AN: 151996 Hom.: 19203 Cov.: 32 AF XY: 0.499 AC XY: 37054 AN XY: 74290

African (AFR) AF: 0.544 AC: 22577 AN: 41472

American (AMR) AF: 0.522 AC: 7976 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3165 AN: 5124

South Asian (SAS) AF: 0.726 AC: 3499 AN: 4820

European-Finnish (FIN) AF: 0.340 AC: 3596 AN: 10586

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31208 AN: 67918

Other (OTH) AF: 0.515 AC: 1087 AN: 2112

Alfa AF: 0.270 Hom.: 486

Bravo AF: 0.506

Asia WGS AF: 0.714 AC: 2481 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.54
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

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: rs1625907; hg19: chr6-29796152; COSMIC: COSV64406204; COSMIC: COSV64406204;