6-29829434-C-T

Variant names:

• chr6-29829434-C-T
• rs41562616
• NM_001384290.1:c.636C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001384290.1(HLA-G):​c.636C>T​(p.His212His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,613,360 control chromosomes in the GnomAD database, including 1,733 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 0.058 (368 hom., cov: 30)
  • Exomes 𝑓: 0.038 (1365 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 7 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-2.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.636C>T	p.His212His	synonymous_variant	Exon 4 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.636C>T	p.His212His	synonymous_variant	Exon 4 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8754 AN: 151950 Hom.: 362 Cov.: 30

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0724

GnomAD2 exomes AF: 0.0456 AC: 11424 AN: 250700 AF XY: 0.0427

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.0757

Gnomad EAS exome AF: 0.00386

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.0351

Gnomad OTH exome AF: 0.0495

GnomAD4 exome AF: 0.0379 AC: 55421 AN: 1461292 Hom.: 1365 Cov.: 36 AF XY: 0.0376 AC XY: 27361 AN XY: 726950

African (AFR) AF: 0.104 AC: 3473 AN: 33460

American (AMR) AF: 0.0943 AC: 4215 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 2016 AN: 26114

East Asian (EAS) AF: 0.00713 AC: 283 AN: 39696

South Asian (SAS) AF: 0.0376 AC: 3239 AN: 86240

European-Finnish (FIN) AF: 0.0126 AC: 674 AN: 53414

Middle Eastern (MID) AF: 0.0869 AC: 501 AN: 5762

European-Non Finnish (NFE) AF: 0.0345 AC: 38391 AN: 1111546

Other (OTH) AF: 0.0436 AC: 2629 AN: 60358

GnomAD4 genome AF: 0.0577 AC: 8774 AN: 152068 Hom.: 368 Cov.: 30 AF XY: 0.0550 AC XY: 4088 AN XY: 74332

African (AFR) AF: 0.103 AC: 4274 AN: 41424

American (AMR) AF: 0.0856 AC: 1307 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.00755 AC: 39 AN: 5166

South Asian (SAS) AF: 0.0291 AC: 140 AN: 4818

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10608

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0361 AC: 2454 AN: 68000

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0365 Hom.: 64

Bravo AF: 0.0671

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.0385

EpiControl AF: 0.0411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.49
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41562616; hg19: chr6-29797211; COSMIC: COSV64405238; COSMIC: COSV64405238;