chr6-29831017-A-G

Variant names:

• chr6-29831017-A-G
• rs9380142
• NM_001384290.1:c.*278A>G

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.*278A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 180,534 control chromosomes in the GnomAD database, including 6,007 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 (5897 hom., cov: 34)
  • Exomes 𝑓: 0.088 (110 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 115 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.*278A>G		3_prime_UTR	Exon 7 of 7	NP_001371219.1
	HLA-G	NM_001363567.2		c.*278A>G		3_prime_UTR	Exon 8 of 8	NP_001350496.1
	HLA-G	NM_001384280.1		c.*278A>G		3_prime_UTR	Exon 9 of 9	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.*278A>G		3_prime_UTR	Exon 7 of 7	ENSP00000353472.6
	HLA-G	ENST00000478355.5	TSL:6	n.1417A>G		non_coding_transcript_exon	Exon 6 of 6
	HLA-G	ENST00000478519.5	TSL:6	n.*326A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000436375.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41505 AN: 152110 Hom.: 5895 Cov.: 34

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.0882 AC: 2498 AN: 28306 Hom.: 110 Cov.: 0 AF XY: 0.0805 AC XY: 1266 AN XY: 15736

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0367 AC: 25 AN: 682

American (AMR) AF: 0.109 AC: 282 AN: 2584

Ashkenazi Jewish (ASJ) AF: 0.0371 AC: 31 AN: 836

East Asian (EAS) AF: 0.0727 AC: 65 AN: 894

South Asian (SAS) AF: 0.0327 AC: 210 AN: 6420

European-Finnish (FIN) AF: 0.131 AC: 85 AN: 650

Middle Eastern (MID) AF: 0.0439 AC: 5 AN: 114

European-Non Finnish (NFE) AF: 0.114 AC: 1685 AN: 14800

Other (OTH) AF: 0.0830 AC: 110 AN: 1326

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.273 AC: 41515 AN: 152228 Hom.: 5897 Cov.: 34 AF XY: 0.272 AC XY: 20232 AN XY: 74438

African (AFR) AF: 0.196 AC: 8141 AN: 41548

American (AMR) AF: 0.250 AC: 3818 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1829 AN: 5190

South Asian (SAS) AF: 0.163 AC: 789 AN: 4830

European-Finnish (FIN) AF: 0.364 AC: 3849 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21514 AN: 67986

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.296 Hom.: 8807

Bravo AF: 0.265

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.59
PhyloP100		-0.67
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: rs9380142; hg19: chr6-29798794;