dbSNP rs115842765: DNPH1:c.*153C>A (chr6-43225580-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006443.3(DNPH1):c.*153C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 785,980 control chromosomes in the GnomAD database, including 187 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 0.023 ( 54 hom., cov: 32)

Exomes 𝑓: 0.018 ( 133 hom. )

Consequence

DNPH1
NM_006443.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Publications

4 publications found

Variant links:

Genes affected

DNPH1 (HGNC:21218): (2'-deoxynucleoside 5'-phosphate N-hydrolase 1) This gene was identified on the basis of its stimulation by c-Myc protein. The latter is a transcription factor that participates in the regulation of cell proliferation, differentiation, and apoptosis. The exact function of this gene is not known but studies in rat suggest a role in cellular proliferation and c-Myc-mediated transformation. Two alternative transcripts encoding different proteins have been described. [provided by RefSeq, Jul 2008]

DNPH1 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=-0.93).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0231 (3517/152236) while in subpopulation AFR AF = 0.0399 (1656/41520). AF 95% confidence interval is 0.0383. There are 54 homozygotes in GnomAd4. There are 1595 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNPH1	NM_006443.3 link	c.*153C>A		downstream_gene_variant		ENST00000230431.11	NP_006434.1
DNPH1	NM_199184.2 link	c.*382C>A		downstream_gene_variant			NP_954653.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
DNPH1	ENST00000230431.11 link	c.*153C>A	downstream_gene_variant	1	NM_006443.3	ENSP00000230431.7
DNPH1	ENST00000509253.5 link	c.*153C>A	downstream_gene_variant	3		ENSP00000422440.1
DNPH1	ENST00000393987.2 link	c.*382C>A	downstream_gene_variant	2		ENSP00000377556.2

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3492

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.0183

AC:

11574

AN:

633744

Hom.:

133

Cov.:

AF XY:

0.0180

AC XY:

5863

AN XY:

326284

show subpopulations

African (AFR)

AF:

0.0379

AC:

613

AN:

16184

American (AMR)

AF:

0.0128

AC:

286

AN:

22384

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

356

AN:

15294

East Asian (EAS)

AF:

0.0131

AC:

422

AN:

32300

South Asian (SAS)

AF:

0.00993

AC:

506

AN:

50976

European-Finnish (FIN)

AF:

0.00272

AC:

AN:

30902

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

2850

European-Non Finnish (NFE)

AF:

0.0198

AC:

8509

AN:

430748

Other (OTH)

AF:

0.0218

AC:

701

AN:

32106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

571

1142

1714

2285

2856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0231

AC:

3517

AN:

152236

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1595

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0399

AC:

1656

AN:

41520

American (AMR)

AF:

0.0190

AC:

291

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3468

East Asian (EAS)

AF:

0.0133

AC:

AN:

5176

South Asian (SAS)

AF:

0.00891

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0191

AC:

1297

AN:

68024

Other (OTH)

AF:

0.0270

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

173

346

520

693

866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0197

Hom.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.7

(source)

DANN

Benign

0.74

PhyloP100

1.6

Splicing

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

Publications

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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