rs2523546

Variant names:

• chr6-31365143-G-A
• rs2523546
• ENST00000696632.1:n.1608C>T

Variant summary

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

The ENST00000696632.1(ENSG00000293281):​n.1608C>T 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 0.0783 in 152,136 control chromosomes in the GnomAD database, including 629 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 0.078 (629 hom., cov: 33)
• Consequence: ENSG00000293281 ENST00000696632.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHFRP2		n.31365143G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293281	ENST00000696632.1	n.1608C>T		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000293281	ENST00000696691.1	n.1609C>T		non_coding_transcript_exon_variant	Exon 2 of 3
ENSG00000293281	ENST00000696692.1	n.498C>T		non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11908 AN: 152018 Hom.: 629 Cov.: 33

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0600

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

GnomAD4 genome AF: 0.0783 AC: 11911 AN: 152136 Hom.: 629 Cov.: 33 AF XY: 0.0740 AC XY: 5503 AN XY: 74404

African (AFR) AF: 0.0371 AC: 1540 AN: 41480

American (AMR) AF: 0.0390 AC: 596 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3470

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5186

South Asian (SAS) AF: 0.0630 AC: 304 AN: 4822

European-Finnish (FIN) AF: 0.0863 AC: 912 AN: 10570

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8104 AN: 68004

Other (OTH) AF: 0.0594 AC: 125 AN: 2106

Alfa AF: 0.0988 Hom.: 110

Bravo AF: 0.0720

Asia WGS AF: 0.0230 AC: 79 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	8.1
DANN	Benign	0.42
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs2523546; hg19: chr6-31332920;