6-29828326-T-C

Variant names:

• chr6-29828326-T-C
• rs1626038
• NM_001384290.1:c.343+10T>C

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_001384290.1(HLA-G):​c.343+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,595,262 control chromosomes in the GnomAD database, including 229,801 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 0.56 (24100 hom., cov: 32)
  • Exomes 𝑓: 0.53 (205701 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.343+10T>C		intron_variant	Intron 2 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.343+10T>C		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84387 AN: 151532 Hom.: 24056 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.584

GnomAD2 exomes AF: 0.551 AC: 134187 AN: 243490 AF XY: 0.559

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.595

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.612

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.529 AC: 763609 AN: 1443610 Hom.: 205701 Cov.: 56 AF XY: 0.537 AC XY: 385268 AN XY: 717808

African (AFR) AF: 0.657 AC: 21929 AN: 33378

American (AMR) AF: 0.605 AC: 26734 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 16862 AN: 25786

East Asian (EAS) AF: 0.672 AC: 26511 AN: 39472

South Asian (SAS) AF: 0.750 AC: 64313 AN: 85730

European-Finnish (FIN) AF: 0.366 AC: 18843 AN: 51532

Middle Eastern (MID) AF: 0.657 AC: 3770 AN: 5736

European-Non Finnish (NFE) AF: 0.502 AC: 550683 AN: 1097994

Other (OTH) AF: 0.568 AC: 33964 AN: 59774

GnomAD4 genome AF: 0.557 AC: 84486 AN: 151652 Hom.: 24100 Cov.: 32 AF XY: 0.555 AC XY: 41146 AN XY: 74074

African (AFR) AF: 0.650 AC: 26907 AN: 41380

American (AMR) AF: 0.609 AC: 9292 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2241 AN: 3464

East Asian (EAS) AF: 0.626 AC: 3195 AN: 5106

South Asian (SAS) AF: 0.755 AC: 3642 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3706 AN: 10514

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33642 AN: 67792

Other (OTH) AF: 0.588 AC: 1238 AN: 2104

Alfa AF: 0.567 Hom.: 14027

Bravo AF: 0.579

Asia WGS AF: 0.741 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.36
PhyloP100		-1.0
PromoterAI		0.014	Neutral
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: rs1626038; hg19: chr6-29796103; COSMIC: COSV64405587;