ENST00000696632.1:n.2699G>A

Variant names:

• chr6-31364052-C-T
• rs2523554
• ENST00000696632.1:n.2699G>A

Variant summary

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

The ENST00000696632.1(ENSG00000293281):​n.2699G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,614 control chromosomes in the GnomAD database, including 38,017 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 0.70 (38017 hom., cov: 30)
• Consequence: ENSG00000293281 ENST00000696632.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 49 publications found

Genes affected

ENSG00000293281 (HGNC:):

DHFRP2 (HGNC:2863): (dihydrofolate reductase pseudogene 2)

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B 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. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHFRP2		n.31364052C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293281	ENST00000696632.1	n.2699G>A		non_coding_transcript_exon_variant	Exon 2 of 2
HLA-B	ENST00000696559.1	c.-204+1691G>A		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-204+1691G>A		intron_variant	Intron 1 of 9			ENSP00000512718.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106273 AN: 151500 Hom.: 37968 Cov.: 30

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.702 AC: 106379 AN: 151614 Hom.: 38017 Cov.: 30 AF XY: 0.710 AC XY: 52543 AN XY: 74026

African (AFR) AF: 0.762 AC: 31483 AN: 41332

American (AMR) AF: 0.820 AC: 12511 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2981 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4250 AN: 5176

South Asian (SAS) AF: 0.837 AC: 4030 AN: 4816

European-Finnish (FIN) AF: 0.642 AC: 6635 AN: 10336

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41977 AN: 67912

Other (OTH) AF: 0.769 AC: 1622 AN: 2108

Alfa AF: 0.653 Hom.: 132819

Bravo AF: 0.716

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.5
DANN	Benign	0.11
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2523554; hg19: chr6-31331829;