chr6-29828480-C-T

Variant names:

• chr6-29828480-C-T
• rs1625035
• NM_001384290.1:c.344-63C>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.344-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,575,594 control chromosomes in the GnomAD database, including 219,134 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 0.54 (22762 hom., cov: 30)
  • Exomes 𝑓: 0.52 (196372 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• 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]

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

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 = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.344-63C>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.344-63C>T		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82206 AN: 151482 Hom.: 22728 Cov.: 30

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.519 AC: 738941 AN: 1423994 Hom.: 196372 Cov.: 49 AF XY: 0.525 AC XY: 370234 AN XY: 704654

African (AFR) AF: 0.615 AC: 19916 AN: 32388

American (AMR) AF: 0.599 AC: 24429 AN: 40778

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 15190 AN: 23324

East Asian (EAS) AF: 0.662 AC: 26085 AN: 39392

South Asian (SAS) AF: 0.709 AC: 56954 AN: 80382

European-Finnish (FIN) AF: 0.360 AC: 18132 AN: 50414

Middle Eastern (MID) AF: 0.648 AC: 3560 AN: 5496

European-Non Finnish (NFE) AF: 0.496 AC: 542199 AN: 1093326

Other (OTH) AF: 0.555 AC: 32476 AN: 58494

GnomAD4 genome AF: 0.543 AC: 82290 AN: 151600 Hom.: 22762 Cov.: 30 AF XY: 0.540 AC XY: 39985 AN XY: 74032

African (AFR) AF: 0.613 AC: 25351 AN: 41322

American (AMR) AF: 0.600 AC: 9150 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2239 AN: 3468

East Asian (EAS) AF: 0.617 AC: 3130 AN: 5070

South Asian (SAS) AF: 0.695 AC: 3348 AN: 4814

European-Finnish (FIN) AF: 0.350 AC: 3680 AN: 10526

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33561 AN: 67842

Other (OTH) AF: 0.578 AC: 1213 AN: 2100

Alfa AF: 0.517 Hom.: 2648

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 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	7.3
DANN	Benign	0.93
PhyloP100		-0.49
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: rs1625035; hg19: chr6-29796257; COSMIC: COSV64405405; COSMIC: COSV64405405;