rs1233334

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-29827120-G-A
• chr6-29827120-G-C
• chr6-29827120-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001363567.2(HLA-G):​c.6+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.6+76G>A		intron_variant	Intron 1 of 7		NP_001350496.1
HLA-G	NM_001384280.1	c.6+76G>A		intron_variant	Intron 2 of 8		NP_001371209.1
HLA-G	NM_002127.6	c.-113+76G>A		intron_variant	Intron 1 of 7		NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+76G>A		intron_variant	Intron 1 of 7	6		ENSP00000366024.2
HLA-G	ENST00000428701.6	n.66+76G>A		intron_variant	Intron 1 of 4	6
HLA-F-AS1	ENST00000849927.1	n.26+1351C>T		intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1	n.230+600C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 325184 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 183830

African (AFR) AF: 0.00 AC: 0 AN: 8930

American (AMR) AF: 0.00 AC: 0 AN: 27760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10818

East Asian (EAS) AF: 0.00 AC: 0 AN: 9932

South Asian (SAS) AF: 0.00 AC: 0 AN: 59962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2788

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 162652

Other (OTH) AF: 0.00 AC: 0 AN: 14676

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.54
PhyloP100		-0.74
PromoterAI		0.18	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;