chr6-29828550-C-T

Variant names:

• chr6-29828550-C-T
• rs1130356
• NM_001384290.1:c.351C>T

Variant summary

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

The ENST00000360323.11(HLA-G):​c.351C>T​(p.His117His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,148 control chromosomes in the GnomAD database, including 80,020 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 0.28 (6277 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73743 hom.)
• Consequence: HLA-G ENST00000360323.11 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 20 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 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.351C>T	p.His117His	synonymous	Exon 3 of 7	NP_001371219.1
	HLA-G	NM_001363567.2		c.366C>T	p.His122His	synonymous	Exon 4 of 8	NP_001350496.1
	HLA-G	NM_001384280.1		c.366C>T	p.His122His	synonymous	Exon 5 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.351C>T	p.His117His	synonymous	Exon 3 of 7	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.366C>T	p.His122His	synonymous	Exon 4 of 8	ENSP00000366024.2
	HLA-G	ENST00000478355.5	TSL:6	n.351C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43228 AN: 151900 Hom.: 6273 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.284 AC: 70029 AN: 246148 AF XY: 0.290

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.0929

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.314 AC: 457897 AN: 1460130 Hom.: 73743 Cov.: 57 AF XY: 0.316 AC XY: 229315 AN XY: 726326

African (AFR) AF: 0.268 AC: 8963 AN: 33468

American (AMR) AF: 0.286 AC: 12767 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 10513 AN: 26096

East Asian (EAS) AF: 0.154 AC: 6115 AN: 39692

South Asian (SAS) AF: 0.337 AC: 29054 AN: 86244

European-Finnish (FIN) AF: 0.218 AC: 11406 AN: 52236

Middle Eastern (MID) AF: 0.346 AC: 1993 AN: 5768

European-Non Finnish (NFE) AF: 0.322 AC: 358149 AN: 1111556

Other (OTH) AF: 0.314 AC: 18937 AN: 60356

GnomAD4 genome AF: 0.285 AC: 43257 AN: 152018 Hom.: 6277 Cov.: 32 AF XY: 0.280 AC XY: 20772 AN XY: 74302

African (AFR) AF: 0.269 AC: 11158 AN: 41460

American (AMR) AF: 0.289 AC: 4409 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3466

East Asian (EAS) AF: 0.113 AC: 579 AN: 5140

South Asian (SAS) AF: 0.296 AC: 1429 AN: 4820

European-Finnish (FIN) AF: 0.212 AC: 2251 AN: 10596

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21102 AN: 67942

Other (OTH) AF: 0.284 AC: 599 AN: 2108

Alfa AF: 0.303 Hom.: 4835

Bravo AF: 0.290

Asia WGS AF: 0.191 AC: 668 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1130356; hg19: chr6-29796327; COSMIC: COSV64405769; COSMIC: COSV64405769;