ENST00000414224.1:n.254A>G

Variant names:

• chr6-31366645-T-C
• rs2844577
• ENST00000414224.1:n.254A>G

Variant summary

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

The ENST00000414224.1(DHFRP2):​n.254A>G 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 0.113 in 1,389,596 control chromosomes in the GnomAD database, including 10,985 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 (630 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10355 hom.)
• Consequence: DHFRP2 ENST00000414224.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 14 publications found

Genes affected

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]

ENSG00000293281 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414224.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHFRP2	ENST00000414224.1	TSL:6	n.254A>G		non_coding_transcript_exon	Exon 1 of 1
	HLA-B	ENST00000474381.2	TSL:6	n.368A>G		non_coding_transcript_exon	Exon 1 of 9
	HLA-B	ENST00000481849.6	TSL:6	n.368A>G		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11905 AN: 152122 Hom.: 630 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00480

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.117 AC: 144982 AN: 1237356 Hom.: 10355 Cov.: 24 AF XY: 0.116 AC XY: 72745 AN XY: 626398

African (AFR) AF: 0.0361 AC: 1032 AN: 28580

American (AMR) AF: 0.0300 AC: 1314 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.0457 AC: 1119 AN: 24490

East Asian (EAS) AF: 0.00145 AC: 56 AN: 38632

South Asian (SAS) AF: 0.0826 AC: 6734 AN: 81494

European-Finnish (FIN) AF: 0.0877 AC: 4644 AN: 52968

Middle Eastern (MID) AF: 0.0471 AC: 249 AN: 5290

European-Non Finnish (NFE) AF: 0.137 AC: 124514 AN: 909424

Other (OTH) AF: 0.101 AC: 5320 AN: 52704

GnomAD4 genome AF: 0.0782 AC: 11909 AN: 152240 Hom.: 630 Cov.: 32 AF XY: 0.0739 AC XY: 5498 AN XY: 74428

African (AFR) AF: 0.0371 AC: 1539 AN: 41534

American (AMR) AF: 0.0387 AC: 592 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3472

East Asian (EAS) AF: 0.00462 AC: 24 AN: 5192

South Asian (SAS) AF: 0.0627 AC: 303 AN: 4830

European-Finnish (FIN) AF: 0.0860 AC: 911 AN: 10594

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

European-Non Finnish (NFE) AF: 0.119 AC: 8103 AN: 68014

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.102 Hom.: 740

Bravo AF: 0.0720

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.83

Splicing

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

Other links and lift over

dbSNP: rs2844577; hg19: chr6-31334422;