6-29828908-T-C

Variant names:

• chr6-29828908-T-C
• rs1632941
• NM_001384290.1:c.619+90T>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+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,520,056 control chromosomes in the GnomAD database, including 180,411 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 (18072 hom., cov: 30)
  • Exomes 𝑓: 0.48 (162339 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 15 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 = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.619+90T>C		intron_variant	Intron 3 of 6	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.619+90T>C		intron_variant	Intron 3 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73500 AN: 151518 Hom.: 18049 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.499

GnomAD4 exome AF: 0.481 AC: 658764 AN: 1368420 Hom.: 162339 AF XY: 0.489 AC XY: 334491 AN XY: 684652

African (AFR) AF: 0.510 AC: 16197 AN: 31746

American (AMR) AF: 0.503 AC: 21765 AN: 43294

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 14301 AN: 25070

East Asian (EAS) AF: 0.656 AC: 25657 AN: 39114

South Asian (SAS) AF: 0.669 AC: 55769 AN: 83320

European-Finnish (FIN) AF: 0.346 AC: 18027 AN: 52046

Middle Eastern (MID) AF: 0.561 AC: 3137 AN: 5596

European-Non Finnish (NFE) AF: 0.460 AC: 474674 AN: 1031028

Other (OTH) AF: 0.511 AC: 29237 AN: 57206

GnomAD4 genome AF: 0.485 AC: 73564 AN: 151636 Hom.: 18072 Cov.: 30 AF XY: 0.485 AC XY: 35953 AN XY: 74098

African (AFR) AF: 0.510 AC: 21051 AN: 41280

American (AMR) AF: 0.514 AC: 7845 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1964 AN: 3462

East Asian (EAS) AF: 0.611 AC: 3127 AN: 5118

South Asian (SAS) AF: 0.667 AC: 3205 AN: 4808

European-Finnish (FIN) AF: 0.340 AC: 3589 AN: 10554

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

European-Non Finnish (NFE) AF: 0.459 AC: 31130 AN: 67846

Other (OTH) AF: 0.505 AC: 1063 AN: 2106

Alfa AF: 0.467 Hom.: 11475

Bravo AF: 0.496

Asia WGS AF: 0.680 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.4
DANN	Benign	0.63
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1632941; hg19: chr6-29796685; COSMIC: COSV64405597; COSMIC: COSV64405597;