rs1632944

Positions:

• chr6-29827212-G-A
• chr6-29827212-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363567.2(HLA-G):​c.6+168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,908 control chromosomes in the GnomAD database, including 18,130 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 (18130 hom., cov: 31)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.6+168G>A		intron_variant			NP_001350496.1
HLA-G	NM_001384280.1	c.6+168G>A		intron_variant			NP_001371209.1
HLA-G	NM_002127.6	c.-113+168G>A		intron_variant			NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+168G>A		intron_variant				ENSP00000366024	A2
HLA-G	ENST00000428701.6	n.66+168G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73682 AN: 151790 Hom.: 18107 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.485 AC: 73746 AN: 151908 Hom.: 18130 Cov.: 31 AF XY: 0.485 AC XY: 36041 AN XY: 74242

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.507

Alfa AF: 0.469 Hom.: 2107

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs1632944; hg19: chr6-29794989; COSMIC: COSV64407030; COSMIC: COSV64407030;