6-29827120-G-T

Variant names:

• chr6-29827120-G-T
• rs1233334
• NM_001363567.2:c.6+76G>T

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+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 477,354 control chromosomes in the GnomAD database, including 804 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 0.058 (372 hom., cov: 32)
  • Exomes 𝑓: 0.041 (432 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 35 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001363567.2		c.6+76G>T		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.6+76G>T		intron	N/A	NP_001371209.1
	HLA-G	NM_002127.6		c.-113+76G>T		intron	N/A	NP_002118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000376828.6	TSL:6	c.6+76G>T		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000428701.6	TSL:6	n.66+76G>T		intron	N/A
	HLA-F-AS1	ENST00000849927.1		n.26+1351C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8780 AN: 152066 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00751

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0412 AC: 13410 AN: 325170 Hom.: 432 AF XY: 0.0397 AC XY: 7303 AN XY: 183826

African (AFR) AF: 0.102 AC: 911 AN: 8930

American (AMR) AF: 0.0928 AC: 2575 AN: 27752

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 828 AN: 10816

East Asian (EAS) AF: 0.00463 AC: 46 AN: 9932

South Asian (SAS) AF: 0.0383 AC: 2294 AN: 59962

European-Finnish (FIN) AF: 0.0120 AC: 333 AN: 27666

Middle Eastern (MID) AF: 0.0940 AC: 262 AN: 2788

European-Non Finnish (NFE) AF: 0.0337 AC: 5489 AN: 162648

Other (OTH) AF: 0.0458 AC: 672 AN: 14676

GnomAD4 genome AF: 0.0578 AC: 8800 AN: 152184 Hom.: 372 Cov.: 32 AF XY: 0.0551 AC XY: 4096 AN XY: 74374

African (AFR) AF: 0.103 AC: 4294 AN: 41508

American (AMR) AF: 0.0857 AC: 1311 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.00753 AC: 39 AN: 5180

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4826

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10556

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0361 AC: 2456 AN: 68020

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.0157 Hom.: 1450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.74
PromoterAI		-0.068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1233334; hg19: chr6-29794897;