NM_001363567.2:c.7-192G>A

Variant names:

• chr6-29827644-G-A
• rs1233333
• NM_001363567.2:c.7-192G>A

Variant summary

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

The NM_001363567.2(HLA-G):​c.7-192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 642,566 control chromosomes in the GnomAD database, including 79,533 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 0.49 (18147 hom., cov: 32)
  • Exomes 𝑓: 0.49 (61386 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363567.2. 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_001363567.2		c.7-192G>A		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.7-192G>A		intron	N/A	NP_001371209.1	Q5RJ85
	HLA-G	NM_002127.6		c.-112-89G>A		intron	N/A	NP_002118.1	P17693-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000376828.6	TSL:6	c.7-192G>A		intron	N/A	ENSP00000366024.2	Q5RJ85
	HCG4P8	ENST00000443049.1	TSL:6	n.721C>T		non_coding_transcript_exon	Exon 1 of 1
	HLA-G	ENST00000428701.6	TSL:6	n.67-89G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73716 AN: 151916 Hom.: 18124 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.488 AC: 239596 AN: 490532 Hom.: 61386 Cov.: 5 AF XY: 0.501 AC XY: 132501 AN XY: 264382

African (AFR) AF: 0.505 AC: 7280 AN: 14402

American (AMR) AF: 0.502 AC: 15758 AN: 31392

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 9047 AN: 15996

East Asian (EAS) AF: 0.651 AC: 17381 AN: 26708

South Asian (SAS) AF: 0.668 AC: 37022 AN: 55448

European-Finnish (FIN) AF: 0.342 AC: 11007 AN: 32192

Middle Eastern (MID) AF: 0.567 AC: 1660 AN: 2928

European-Non Finnish (NFE) AF: 0.447 AC: 127238 AN: 284898

Other (OTH) AF: 0.497 AC: 13203 AN: 26568

GnomAD4 genome AF: 0.485 AC: 73780 AN: 152034 Hom.: 18147 Cov.: 32 AF XY: 0.485 AC XY: 36066 AN XY: 74322

African (AFR) AF: 0.510 AC: 21170 AN: 41488

American (AMR) AF: 0.515 AC: 7869 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3472

East Asian (EAS) AF: 0.611 AC: 3145 AN: 5150

South Asian (SAS) AF: 0.667 AC: 3213 AN: 4816

European-Finnish (FIN) AF: 0.340 AC: 3601 AN: 10584

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31155 AN: 67922

Other (OTH) AF: 0.506 AC: 1066 AN: 2108

Alfa AF: 0.472 Hom.: 16415

Bravo AF: 0.496

Asia WGS AF: 0.684 AC: 2381 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	2.6
DANN	Benign	0.78
PhyloP100		-0.93
PromoterAI		-0.015	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: rs1233333; hg19: chr6-29795421; COSMIC: COSV64406088; COSMIC: COSV64406088;