rs1632942

Variant names:

• chr6-29828863-T-C
• rs1632942
• NM_001384290.1:c.619+45T>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.619+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,605,552 control chromosomes in the GnomAD database, including 225,030 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 0.55 (22833 hom., cov: 30)
  • Exomes 𝑓: 0.52 (202197 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.619+45T>C		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.634+45T>C		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.634+45T>C		intron	N/A	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.619+45T>C		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.634+45T>C		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.343+547T>C		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82404 AN: 150738 Hom.: 22799 Cov.: 30

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.578

GnomAD2 exomes AF: 0.544 AC: 134474 AN: 247242 AF XY: 0.550

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.522 AC: 759111 AN: 1454694 Hom.: 202197 Cov.: 37 AF XY: 0.528 AC XY: 382554 AN XY: 723926

African (AFR) AF: 0.616 AC: 20587 AN: 33418

American (AMR) AF: 0.599 AC: 26712 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 16990 AN: 26064

East Asian (EAS) AF: 0.663 AC: 26287 AN: 39666

South Asian (SAS) AF: 0.710 AC: 61166 AN: 86182

European-Finnish (FIN) AF: 0.360 AC: 19088 AN: 53048

Middle Eastern (MID) AF: 0.650 AC: 3745 AN: 5758

European-Non Finnish (NFE) AF: 0.498 AC: 550979 AN: 1105728

Other (OTH) AF: 0.557 AC: 33557 AN: 60238

GnomAD4 genome AF: 0.547 AC: 82488 AN: 150858 Hom.: 22833 Cov.: 30 AF XY: 0.544 AC XY: 40106 AN XY: 73704

African (AFR) AF: 0.617 AC: 25402 AN: 41196

American (AMR) AF: 0.603 AC: 9173 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2238 AN: 3458

East Asian (EAS) AF: 0.622 AC: 3173 AN: 5098

South Asian (SAS) AF: 0.698 AC: 3350 AN: 4796

European-Finnish (FIN) AF: 0.355 AC: 3711 AN: 10446

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33602 AN: 67380

Other (OTH) AF: 0.583 AC: 1217 AN: 2086

Alfa AF: 0.523 Hom.: 62337

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.23
PhyloP100		-1.2
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: rs1632942; hg19: chr6-29796640; COSMIC: COSV64405850; COSMIC: COSV64405850;