6-29830005-T-C

Variant names:

• chr6-29830005-T-C
• rs1611627
• NM_001384290.1:c.1012+73T>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.1012+73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,079,498 control chromosomes in the GnomAD database, including 90,737 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 0.43 (14491 hom., cov: 31)
  • Exomes 𝑓: 0.40 (76246 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 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.1012+73T>C		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.1027+73T>C		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.1027+73T>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.1012+73T>C		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.1027+73T>C		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.1012+73T>C		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65658 AN: 151784 Hom.: 14467 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.398 AC: 369057 AN: 927596 Hom.: 76246 AF XY: 0.404 AC XY: 192928 AN XY: 476986

African (AFR) AF: 0.489 AC: 11115 AN: 22726

American (AMR) AF: 0.462 AC: 17202 AN: 37264

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 9492 AN: 18836

East Asian (EAS) AF: 0.550 AC: 20494 AN: 37250

South Asian (SAS) AF: 0.511 AC: 34202 AN: 66962

European-Finnish (FIN) AF: 0.307 AC: 15641 AN: 50952

Middle Eastern (MID) AF: 0.486 AC: 2236 AN: 4598

European-Non Finnish (NFE) AF: 0.372 AC: 240860 AN: 646718

Other (OTH) AF: 0.421 AC: 17815 AN: 42290

GnomAD4 genome AF: 0.433 AC: 65716 AN: 151902 Hom.: 14491 Cov.: 31 AF XY: 0.430 AC XY: 31941 AN XY: 74264

African (AFR) AF: 0.498 AC: 20623 AN: 41446

American (AMR) AF: 0.470 AC: 7172 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2128 AN: 5110

South Asian (SAS) AF: 0.500 AC: 2413 AN: 4824

European-Finnish (FIN) AF: 0.300 AC: 3179 AN: 10580

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27000 AN: 67896

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.421 Hom.: 1764

Bravo AF: 0.447

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.023
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: rs1611627; hg19: chr6-29797782; COSMIC: COSV64407049;