6-29828032-C-T

Variant names:

• chr6-29828032-C-T
• rs1628628
• NM_001384290.1:c.74-15C>T

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.74-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,599,672 control chromosomes in the GnomAD database, including 129,446 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 0.42 (12625 hom., cov: 31)
  • Exomes 𝑓: 0.41 (116821 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.74-15C>T		intron_variant	Intron 1 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.74-15C>T		intron_variant	Intron 1 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.419 AC: 62875 AN: 149914 Hom.: 12603 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.422 AC: 98711 AN: 234186 AF XY: 0.425

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.460

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.408 AC: 590986 AN: 1449644 Hom.: 116821 Cov.: 69 AF XY: 0.411 AC XY: 296473 AN XY: 720630

African (AFR) AF: 0.453 AC: 14839 AN: 32790

American (AMR) AF: 0.432 AC: 18989 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 12860 AN: 25834

East Asian (EAS) AF: 0.499 AC: 19373 AN: 38832

South Asian (SAS) AF: 0.501 AC: 42743 AN: 85290

European-Finnish (FIN) AF: 0.304 AC: 15752 AN: 51742

Middle Eastern (MID) AF: 0.490 AC: 2346 AN: 4792

European-Non Finnish (NFE) AF: 0.396 AC: 438625 AN: 1106814

Other (OTH) AF: 0.427 AC: 25459 AN: 59626

GnomAD4 genome AF: 0.419 AC: 62929 AN: 150028 Hom.: 12625 Cov.: 31 AF XY: 0.418 AC XY: 30623 AN XY: 73342

African (AFR) AF: 0.468 AC: 18867 AN: 40352

American (AMR) AF: 0.457 AC: 6905 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1724 AN: 3434

East Asian (EAS) AF: 0.394 AC: 1965 AN: 4986

South Asian (SAS) AF: 0.488 AC: 2316 AN: 4742

European-Finnish (FIN) AF: 0.299 AC: 3157 AN: 10542

Middle Eastern (MID) AF: 0.528 AC: 153 AN: 290

European-Non Finnish (NFE) AF: 0.394 AC: 26626 AN: 67598

Other (OTH) AF: 0.429 AC: 887 AN: 2068

Alfa AF: 0.421 Hom.: 2267

Asia WGS AF: 0.521 AC: 1811 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		-0.44
PromoterAI		0.0023	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: rs1628628; hg19: chr6-29795809; COSMIC: COSV64405263;