6-29828329-G-T

Variant names:

• chr6-29828329-G-T
• rs17875399
• NM_001384290.1:c.343+13G>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.343+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,597,234 control chromosomes in the GnomAD database, including 1,741 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 0.062 (374 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1367 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.343+13G>T		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+13G>T		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 8859 AN: 143566 Hom.: 369 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.00834

Gnomad SAS AF: 0.0343

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0780

GnomAD2 exomes AF: 0.0464 AC: 11105 AN: 239304 AF XY: 0.0436

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0935

Gnomad ASJ exome AF: 0.0785

Gnomad EAS exome AF: 0.00385

Gnomad FIN exome AF: 0.0118

Gnomad NFE exome AF: 0.0357

Gnomad OTH exome AF: 0.0503

GnomAD4 exome AF: 0.0381 AC: 55313 AN: 1453550 Hom.: 1367 Cov.: 55 AF XY: 0.0378 AC XY: 27274 AN XY: 722210

African (AFR) AF: 0.106 AC: 3526 AN: 33352

American (AMR) AF: 0.0941 AC: 4184 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 1985 AN: 25614

East Asian (EAS) AF: 0.00705 AC: 279 AN: 39600

South Asian (SAS) AF: 0.0377 AC: 3215 AN: 85256

European-Finnish (FIN) AF: 0.0127 AC: 666 AN: 52408

Middle Eastern (MID) AF: 0.0872 AC: 499 AN: 5720

European-Non Finnish (NFE) AF: 0.0346 AC: 38344 AN: 1107144

Other (OTH) AF: 0.0436 AC: 2615 AN: 60008

GnomAD4 genome AF: 0.0618 AC: 8878 AN: 143684 Hom.: 374 Cov.: 33 AF XY: 0.0591 AC XY: 4140 AN XY: 70054

African (AFR) AF: 0.115 AC: 4372 AN: 38082

American (AMR) AF: 0.0919 AC: 1313 AN: 14292

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 268 AN: 3346

East Asian (EAS) AF: 0.00836 AC: 39 AN: 4664

South Asian (SAS) AF: 0.0348 AC: 139 AN: 3998

European-Finnish (FIN) AF: 0.0109 AC: 112 AN: 10282

Middle Eastern (MID) AF: 0.100 AC: 28 AN: 280

European-Non Finnish (NFE) AF: 0.0372 AC: 2453 AN: 65876

Other (OTH) AF: 0.0771 AC: 153 AN: 1984

Alfa AF: 0.0240 Hom.: 21

Bravo AF: 0.0676

Asia WGS AF: 0.0270 AC: 93 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	7.9
DANN	Benign	0.71
PhyloP100		0.0010
PromoterAI		-0.044	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: rs17875399; hg19: chr6-29796106;