rs1632932

Variant names:

• chr6-29830262-G-A
• rs1632932
• NM_001384290.1:c.1013-116G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-29830262-G-A
• chr6-29830262-G-T

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.1013-116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,128,084 control chromosomes in the GnomAD database, including 123,042 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 (18087 hom., cov: 30)
  • Exomes 𝑓: 0.45 (104955 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. 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_001384290.1	MANE Select	c.1013-116G>A		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.1028-116G>A		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.1028-116G>A		intron	N/A	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.1013-116G>A		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.1028-116G>A		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.1013-116G>A		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73556 AN: 151658 Hom.: 18064 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.452 AC: 441633 AN: 976308 Hom.: 104955 AF XY: 0.465 AC XY: 235539 AN XY: 506514

African (AFR) AF: 0.484 AC: 11432 AN: 23620

American (AMR) AF: 0.502 AC: 21919 AN: 43664

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 12845 AN: 22760

East Asian (EAS) AF: 0.654 AC: 24378 AN: 37262

South Asian (SAS) AF: 0.663 AC: 50057 AN: 75470

European-Finnish (FIN) AF: 0.346 AC: 18338 AN: 52984

Middle Eastern (MID) AF: 0.548 AC: 2631 AN: 4798

European-Non Finnish (NFE) AF: 0.415 AC: 278622 AN: 671658

Other (OTH) AF: 0.486 AC: 21411 AN: 44092

GnomAD4 genome AF: 0.485 AC: 73620 AN: 151776 Hom.: 18087 Cov.: 30 AF XY: 0.485 AC XY: 35960 AN XY: 74148

African (AFR) AF: 0.510 AC: 21082 AN: 41354

American (AMR) AF: 0.514 AC: 7846 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1969 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3148 AN: 5156

South Asian (SAS) AF: 0.666 AC: 3193 AN: 4794

European-Finnish (FIN) AF: 0.340 AC: 3592 AN: 10556

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

European-Non Finnish (NFE) AF: 0.459 AC: 31132 AN: 67880

Other (OTH) AF: 0.506 AC: 1065 AN: 2104

Alfa AF: 0.472 Hom.: 2198

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		-0.086
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1632932; hg19: chr6-29798039; COSMIC: COSV64406459; COSMIC: COSV64406459;