rs1632947

Variant names:

• chr6-29826881-G-A
• rs1632947
• NM_001384280.1:c.-36-122G>A

Variant summary

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

The NM_001384280.1(HLA-G):​c.-36-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 422,470 control chromosomes in the GnomAD database, including 53,524 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 0.49 (18125 hom., cov: 31)
  • Exomes 𝑓: 0.50 (35399 hom.)
• Consequence: HLA-G NM_001384280.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384280.1. 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-G	NM_001384280.1		c.-36-122G>A		intron	N/A	NP_001371209.1	Q5RJ85
	HLA-G	NM_001363567.2		c.-158G>A		upstream_gene	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_002127.6		c.-276G>A		upstream_gene	N/A	NP_002118.1	P17693-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-F-AS1	ENST00000849927.1		n.26+1590C>T		intron	N/A
	HLA-F-AS1	ENST00000849935.1		n.230+839C>T		intron	N/A
	HLA-G	ENST00000376828.6	TSL:6	c.-158G>A		upstream_gene	N/A	ENSP00000366024.2	Q5RJ85

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73664 AN: 151810 Hom.: 18102 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.499 AC: 135035 AN: 270542 Hom.: 35399 AF XY: 0.520 AC XY: 78373 AN XY: 150812

African (AFR) AF: 0.508 AC: 3653 AN: 7188

American (AMR) AF: 0.502 AC: 10723 AN: 21340

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 4514 AN: 8010

East Asian (EAS) AF: 0.602 AC: 5241 AN: 8706

South Asian (SAS) AF: 0.666 AC: 34289 AN: 51506

European-Finnish (FIN) AF: 0.342 AC: 8229 AN: 24064

Middle Eastern (MID) AF: 0.524 AC: 1350 AN: 2576

European-Non Finnish (NFE) AF: 0.452 AC: 60971 AN: 134894

Other (OTH) AF: 0.495 AC: 6065 AN: 12258

GnomAD4 genome AF: 0.485 AC: 73727 AN: 151928 Hom.: 18125 Cov.: 31 AF XY: 0.485 AC XY: 36043 AN XY: 74260

African (AFR) AF: 0.510 AC: 21110 AN: 41382

American (AMR) AF: 0.515 AC: 7859 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3155 AN: 5166

South Asian (SAS) AF: 0.665 AC: 3204 AN: 4818

European-Finnish (FIN) AF: 0.341 AC: 3588 AN: 10534

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31187 AN: 67980

Other (OTH) AF: 0.507 AC: 1067 AN: 2104

Alfa AF: 0.472 Hom.: 2188

Bravo AF: 0.496

Asia WGS AF: 0.683 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.97
DANN	Benign	0.75
PhyloP100		-0.65
PromoterAI		-0.030	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1632947; hg19: chr6-29794658; COSMIC: COSV64405568;