rs1630223

Variant names:

• chr6-29827859-G-A
• rs1630223
• NM_001384290.1:c.15G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-29827859-G-A
• chr6-29827859-G-C
• chr6-29827859-G-T

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.15G>A​(p.Ala5Ala) 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 1,608,764 control chromosomes in the GnomAD database, including 191,867 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 (18029 hom., cov: 29)
  • Exomes 𝑓: 0.48 (173838 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 22 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=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.084 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.15G>A	p.Ala5Ala	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.15G>A	p.Ala5Ala	synonymous_variant	Exon 1 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73396 AN: 151412 Hom.: 18006 Cov.: 29

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.497

GnomAD2 exomes AF: 0.498 AC: 123579 AN: 248306 AF XY: 0.507

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.575

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: 701856 AN: 1457234 Hom.: 173838 Cov.: 43 AF XY: 0.489 AC XY: 354368 AN XY: 725122

African (AFR) AF: 0.511 AC: 17089 AN: 33410

American (AMR) AF: 0.503 AC: 22504 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 14973 AN: 26086

East Asian (EAS) AF: 0.655 AC: 26002 AN: 39676

South Asian (SAS) AF: 0.672 AC: 57879 AN: 86142

European-Finnish (FIN) AF: 0.346 AC: 18339 AN: 52970

Middle Eastern (MID) AF: 0.563 AC: 3228 AN: 5738

European-Non Finnish (NFE) AF: 0.461 AC: 510988 AN: 1108276

Other (OTH) AF: 0.512 AC: 30854 AN: 60234

GnomAD4 genome AF: 0.485 AC: 73460 AN: 151530 Hom.: 18029 Cov.: 29 AF XY: 0.485 AC XY: 35880 AN XY: 74022

African (AFR) AF: 0.510 AC: 21065 AN: 41290

American (AMR) AF: 0.514 AC: 7851 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1966 AN: 3466

East Asian (EAS) AF: 0.609 AC: 3080 AN: 5060

South Asian (SAS) AF: 0.666 AC: 3193 AN: 4792

European-Finnish (FIN) AF: 0.339 AC: 3573 AN: 10536

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

European-Non Finnish (NFE) AF: 0.458 AC: 31088 AN: 67826

Other (OTH) AF: 0.502 AC: 1054 AN: 2098

Alfa AF: 0.482 Hom.: 11436

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	-0.69
CADD	Benign	9.7
DANN	Benign	0.93
PhyloP100		-0.084
PromoterAI		-0.22	Neutral
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: rs1630223; hg19: chr6-29795636; COSMIC: COSV64405573;