rs62391965

Positions:

• chr6-29828972-C-A
• chr6-29828972-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384290.1(HLA-G):​c.619+154C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 152,086 control chromosomes in the GnomAD database, including 370 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 0.052 (370 hom., cov: 31)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.619+154C>A		intron_variant		ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.619+154C>A		intron_variant			NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7883 AN: 151968 Hom.: 368 Cov.: 31

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0518 AC: 7884 AN: 152086 Hom.: 370 Cov.: 31 AF XY: 0.0542 AC XY: 4033 AN XY: 74342

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0607

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0431 Hom.: 25

Bravo AF: 0.0482

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs62391965; hg19: chr6-29796749;