chr6-29827991-T-C

Variant names:

• chr6-29827991-T-C
• rs1629329
• NM_001384290.1:c.74-56T>C

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.74-56T>C 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 1,591,428 control chromosomes in the GnomAD database, including 221,350 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 (22773 hom., cov: 30)
  • Exomes 𝑓: 0.52 (198577 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.74-56T>C		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.89-56T>C		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.89-56T>C		intron	N/A	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.74-56T>C		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.89-56T>C		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.74-56T>C		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82265 AN: 151470 Hom.: 22737 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.519 AC: 746936 AN: 1439840 Hom.: 198577 Cov.: 50 AF XY: 0.525 AC XY: 375237 AN XY: 714374

African (AFR) AF: 0.614 AC: 20285 AN: 33022

American (AMR) AF: 0.595 AC: 25523 AN: 42892

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 16127 AN: 24816

East Asian (EAS) AF: 0.664 AC: 26117 AN: 39340

South Asian (SAS) AF: 0.710 AC: 59039 AN: 83194

European-Finnish (FIN) AF: 0.358 AC: 18079 AN: 50546

Middle Eastern (MID) AF: 0.663 AC: 3123 AN: 4710

European-Non Finnish (NFE) AF: 0.495 AC: 545778 AN: 1102128

Other (OTH) AF: 0.555 AC: 32865 AN: 59192

GnomAD4 genome AF: 0.543 AC: 82351 AN: 151588 Hom.: 22773 Cov.: 30 AF XY: 0.540 AC XY: 40043 AN XY: 74086

African (AFR) AF: 0.614 AC: 25347 AN: 41302

American (AMR) AF: 0.600 AC: 9164 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2235 AN: 3466

East Asian (EAS) AF: 0.620 AC: 3138 AN: 5062

South Asian (SAS) AF: 0.698 AC: 3353 AN: 4802

European-Finnish (FIN) AF: 0.351 AC: 3703 AN: 10542

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33578 AN: 67832

Other (OTH) AF: 0.576 AC: 1213 AN: 2106

Alfa AF: 0.517 Hom.: 2651

Bravo AF: 0.563

Asia WGS AF: 0.711 AC: 2461 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.69
PhyloP100		-2.9
PromoterAI		-0.014	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: rs1629329; hg19: chr6-29795768;