chr6-29827974-C-T

Variant names:

• chr6-29827974-C-T
• rs6932596
• NM_001384290.1:c.73+57C>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.73+57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,586,706 control chromosomes in the GnomAD database, including 73,931 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 0.27 (5890 hom., cov: 31)
  • Exomes 𝑓: 0.30 (68041 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• 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]

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 (EAS) allele frequency at 95% confidence interval = 0.336 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.73+57C>T		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.88+57C>T		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.88+57C>T		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.73+57C>T		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.88+57C>T		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.73+57C>T		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41001 AN: 151606 Hom.: 5887 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.303 AC: 434777 AN: 1434982 Hom.: 68041 Cov.: 49 AF XY: 0.299 AC XY: 212657 AN XY: 711582

African (AFR) AF: 0.164 AC: 5402 AN: 32892

American (AMR) AF: 0.295 AC: 12384 AN: 42020

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5301 AN: 24206

East Asian (EAS) AF: 0.320 AC: 12593 AN: 39378

South Asian (SAS) AF: 0.167 AC: 13726 AN: 81996

European-Finnish (FIN) AF: 0.371 AC: 18685 AN: 50346

Middle Eastern (MID) AF: 0.185 AC: 862 AN: 4654

European-Non Finnish (NFE) AF: 0.318 AC: 349650 AN: 1100550

Other (OTH) AF: 0.274 AC: 16174 AN: 58940

GnomAD4 genome AF: 0.270 AC: 41010 AN: 151724 Hom.: 5890 Cov.: 31 AF XY: 0.270 AC XY: 19968 AN XY: 74090

African (AFR) AF: 0.176 AC: 7311 AN: 41454

American (AMR) AF: 0.248 AC: 3792 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3466

East Asian (EAS) AF: 0.350 AC: 1780 AN: 5086

South Asian (SAS) AF: 0.171 AC: 821 AN: 4804

European-Finnish (FIN) AF: 0.366 AC: 3854 AN: 10524

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21829 AN: 67818

Other (OTH) AF: 0.243 AC: 511 AN: 2100

Alfa AF: 0.153 Hom.: 321

Bravo AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.12
PromoterAI		0.038	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: rs6932596; hg19: chr6-29795751;