NM_001363567.2:c.6+85T>G

Variant names:

• chr6-29827129-T-G
• rs2249863
• NM_001363567.2:c.6+85T>G

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.6+85T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 473,724 control chromosomes in the GnomAD database, including 60,840 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 (18138 hom., cov: 32)
  • Exomes 𝑓: 0.50 (42702 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 25 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]

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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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.6+85T>G		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.6+85T>G		intron	N/A	NP_001371209.1	Q5RJ85
	HLA-G	NM_002127.6		c.-113+85T>G		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.6+85T>G		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000428701.6	TSL:6	n.66+85T>G		intron	N/A
	HLA-F-AS1	ENST00000849927.1		n.26+1342A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73704 AN: 151960 Hom.: 18115 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.504 AC: 162051 AN: 321646 Hom.: 42702 AF XY: 0.523 AC XY: 95066 AN XY: 181748

African (AFR) AF: 0.515 AC: 4512 AN: 8756

American (AMR) AF: 0.505 AC: 13827 AN: 27406

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 6173 AN: 10794

East Asian (EAS) AF: 0.608 AC: 5825 AN: 9584

South Asian (SAS) AF: 0.670 AC: 40075 AN: 59824

European-Finnish (FIN) AF: 0.343 AC: 9349 AN: 27234

Middle Eastern (MID) AF: 0.538 AC: 1490 AN: 2772

European-Non Finnish (NFE) AF: 0.457 AC: 73523 AN: 160774

Other (OTH) AF: 0.502 AC: 7277 AN: 14502

GnomAD4 genome AF: 0.485 AC: 73768 AN: 152078 Hom.: 18138 Cov.: 32 AF XY: 0.485 AC XY: 36046 AN XY: 74320

African (AFR) AF: 0.510 AC: 21148 AN: 41460

American (AMR) AF: 0.514 AC: 7854 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1964 AN: 3464

East Asian (EAS) AF: 0.611 AC: 3160 AN: 5170

South Asian (SAS) AF: 0.666 AC: 3215 AN: 4826

European-Finnish (FIN) AF: 0.340 AC: 3592 AN: 10576

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

European-Non Finnish (NFE) AF: 0.459 AC: 31174 AN: 67984

Other (OTH) AF: 0.505 AC: 1068 AN: 2114

Alfa AF: 0.477 Hom.: 9519

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.21
PhyloP100		-3.4
PromoterAI		-0.029	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: rs2249863; hg19: chr6-29794906;