6-29827880-G-A

Variant names:

• chr6-29827880-G-A
• rs1630185
• NM_001384290.1:c.36G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001384290.1(HLA-G):​c.36G>A​(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,609,910 control chromosomes in the GnomAD database, including 191,836 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 0.48 (18013 hom., cov: 30)
  • Exomes 𝑓: 0.48 (173823 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 24 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]

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

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.169 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.36G>A	p.Leu12Leu	synonymous_variant	Exon 1 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73367 AN: 151460 Hom.: 17990 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.498 AC: 123458 AN: 248076 AF XY: 0.507

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.599

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.482 AC: 702402 AN: 1458332 Hom.: 173823 Cov.: 47 AF XY: 0.489 AC XY: 354620 AN XY: 725636

African (AFR) AF: 0.511 AC: 17086 AN: 33406

American (AMR) AF: 0.503 AC: 22474 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 14964 AN: 26074

East Asian (EAS) AF: 0.655 AC: 26002 AN: 39672

South Asian (SAS) AF: 0.672 AC: 57891 AN: 86172

European-Finnish (FIN) AF: 0.346 AC: 18341 AN: 52962

Middle Eastern (MID) AF: 0.562 AC: 3220 AN: 5726

European-Non Finnish (NFE) AF: 0.461 AC: 511546 AN: 1109388

Other (OTH) AF: 0.512 AC: 30878 AN: 60278

GnomAD4 genome AF: 0.484 AC: 73431 AN: 151578 Hom.: 18013 Cov.: 30 AF XY: 0.484 AC XY: 35856 AN XY: 74042

African (AFR) AF: 0.510 AC: 21067 AN: 41336

American (AMR) AF: 0.513 AC: 7837 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1960 AN: 3462

East Asian (EAS) AF: 0.609 AC: 3078 AN: 5052

South Asian (SAS) AF: 0.666 AC: 3188 AN: 4786

European-Finnish (FIN) AF: 0.338 AC: 3564 AN: 10544

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31087 AN: 67828

Other (OTH) AF: 0.503 AC: 1060 AN: 2106

Alfa AF: 0.477 Hom.: 7590

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2382 AN: 3478

EpiCase AF: 0.490

EpiControl AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		0.17
PromoterAI		-0.052	Neutral
Mutation Taster		=99/1	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: rs1630185; hg19: chr6-29795657; COSMIC: COSV64405578;