6-29827083-C-T

Position:

• chr6-29827083-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363567.2(HLA-G):​c.6+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 502,108 control chromosomes in the GnomAD database, including 63,816 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 0.49 (18134 hom., cov: 32)
  • Exomes 𝑓: 0.50 (45682 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.6+39C>T		intron_variant			NP_001350496.1
HLA-G	NM_001384280.1	c.6+39C>T		intron_variant			NP_001371209.1
HLA-G	NM_002127.6	c.-113+39C>T		intron_variant			NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+39C>T		intron_variant		6		ENSP00000366024.2
HLA-G	ENST00000428701.6	n.66+39C>T		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73691 AN: 151866 Hom.: 18111 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.498 AC: 97450 AN: 195746 Hom.: 25127 AF XY: 0.507 AC XY: 53748 AN XY: 105988

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.503

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.600

Gnomad SAS exome AF: 0.672

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.499 AC: 174810 AN: 350124 Hom.: 45682 Cov.: 0 AF XY: 0.517 AC XY: 102529 AN XY: 198316

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.485 AC: 73754 AN: 151984 Hom.: 18134 Cov.: 32 AF XY: 0.485 AC XY: 36040 AN XY: 74258

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.506

Alfa AF: 0.479 Hom.: 3181

Bravo AF: 0.496

Asia WGS AF: 0.682 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1632946; hg19: chr6-29794860; COSMIC: COSV64405753; COSMIC: COSV64405753;