Genetic Variant DHFRP2:n.254A>G (chr6-31366645-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.831

Publications

14 publications found

Variant links:

Genes affected

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

DHFRP2 links:

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]

HLA-B links:

ENSG00000293281 (HGNC:):

ENSG00000293281 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHFRP2		n.31366645T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
DHFRP2	ENST00000414224.1 link	n.254A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
HLA-B	ENST00000474381.2 link	n.368A>G	non_coding_transcript_exon_variant	Exon 1 of 9	6
HLA-B	ENST00000481849.6 link	n.368A>G	non_coding_transcript_exon_variant	Exon 1 of 8	6

Frequencies

GnomAD3 genomes

AF:

0.0783

AC:

11905

AN:

152122

Hom.:

630

Cov.:

show subpopulations

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.:

AF XY:

0.116

AC XY:

72745

AN XY:

626398

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

6361

12722

19082

25443

31804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0782

AC:

11909

AN:

152240

Hom.:

630

Cov.:

AF XY:

0.0739

AC XY:

5498

AN XY:

74428

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8103

AN:

68014

Other (OTH)

AF:

0.0611

AC:

129

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

553

1107

1660

2214

2767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.102

Hom.:

740

Bravo

AF:

0.0720

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.83

Splicing

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

Publications

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6-31366645-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over