6-29827970-G-C

Variant names:

• chr6-29827970-G-C
• rs6932888
• NM_001384290.1:c.73+53G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360323.11(HLA-G):​c.73+53G>C 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 1,586,400 control chromosomes in the GnomAD database, including 73,869 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 (5889 hom., cov: 31)
  • Exomes 𝑓: 0.30 (67980 hom.)
• Consequence: HLA-G ENST00000360323.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360323.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.73+53G>C		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.88+53G>C		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.88+53G>C		intron	N/A	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.73+53G>C		intron	N/A	ENSP00000353472.6
	HCG4P8	ENST00000443049.1	TSL:6	n.395C>G		non_coding_transcript_exon	Exon 1 of 1
	HLA-G	ENST00000376828.6	TSL:6	c.88+53G>C		intron	N/A	ENSP00000366024.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 40998 AN: 151496 Hom.: 5886 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.303 AC: 434545 AN: 1434788 Hom.: 67980 Cov.: 48 AF XY: 0.299 AC XY: 212510 AN XY: 711400

African (AFR) AF: 0.164 AC: 5395 AN: 32864

American (AMR) AF: 0.294 AC: 12377 AN: 42046

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5274 AN: 24148

East Asian (EAS) AF: 0.320 AC: 12596 AN: 39376

South Asian (SAS) AF: 0.167 AC: 13693 AN: 81908

European-Finnish (FIN) AF: 0.370 AC: 18663 AN: 50378

Middle Eastern (MID) AF: 0.184 AC: 858 AN: 4656

European-Non Finnish (NFE) AF: 0.318 AC: 349527 AN: 1100462

Other (OTH) AF: 0.274 AC: 16162 AN: 58950

GnomAD4 genome AF: 0.270 AC: 41006 AN: 151612 Hom.: 5889 Cov.: 31 AF XY: 0.270 AC XY: 19964 AN XY: 74016

African (AFR) AF: 0.177 AC: 7309 AN: 41372

American (AMR) AF: 0.249 AC: 3796 AN: 15250

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

East Asian (EAS) AF: 0.350 AC: 1773 AN: 5064

South Asian (SAS) AF: 0.171 AC: 821 AN: 4788

European-Finnish (FIN) AF: 0.366 AC: 3857 AN: 10540

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

European-Non Finnish (NFE) AF: 0.322 AC: 21827 AN: 67836

Other (OTH) AF: 0.244 AC: 511 AN: 2096

Alfa AF: 0.296 Hom.: 787

Bravo AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.6
DANN	Benign	0.37
PhyloP100		0.17
PromoterAI		0.0042	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: rs6932888; hg19: chr6-29795747;