dbSNP rs12261515: DRGX:c.526+15G>T (chr10-49386463-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001276451.2(DRGX):c.526+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,531,210 control chromosomes in the GnomAD database, including 45,641 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 0.25 ( 5014 hom., cov: 32)

Exomes 𝑓: 0.24 ( 40627 hom. )

Consequence

DRGX
NM_001276451.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.33

Publications

5 publications found

Variant links:

Genes affected

DRGX (HGNC:21536): (dorsal root ganglia homeobox) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including detection of temperature stimulus; nervous system development; and sensory perception of mechanical stimulus. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

DRGX links:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRGX	NM_001276451.2 link	c.526+15G>T		intron_variant	Intron 6 of 6	ENST00000374139.8	NP_001263380.1	A6NNA5
DRGX	XM_011540089.4 link	c.631+15G>T		intron_variant	Intron 6 of 6		XP_011538391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRGX	ENST00000374139.8 link	c.526+15G>T		intron_variant	Intron 6 of 6	2	NM_001276451.2	ENSP00000363254.1		A6NNA5

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37895

AN:

151892

Hom.:

5006

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.518

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.267

AC:

39291

AN:

147378

AF XY:

0.264

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.543

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.237

AC:

327554

AN:

1379200

Hom.:

40627

Cov.:

AF XY:

0.237

AC XY:

160590

AN XY:

678718

show subpopulations

African (AFR)

AF:

0.254

AC:

7847

AN:

30936

American (AMR)

AF:

0.250

AC:

8055

AN:

32162

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4291

AN:

23372

East Asian (EAS)

AF:

0.487

AC:

17576

AN:

36102

South Asian (SAS)

AF:

0.232

AC:

17436

AN:

75268

European-Finnish (FIN)

AF:

0.283

AC:

13892

AN:

49004

Middle Eastern (MID)

AF:

0.248

AC:

1127

AN:

4548

European-Non Finnish (NFE)

AF:

0.228

AC:

243752

AN:

1070782

Other (OTH)

AF:

0.238

AC:

13578

AN:

57026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13377

26755

40132

53510

66887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8696

17392

26088

34784

43480

<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:

0.249

AC:

37925

AN:

152010

Hom.:

5014

Cov.:

AF XY:

0.252

AC XY:

18684

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.255

AC:

10578

AN:

41444

American (AMR)

AF:

0.251

AC:

3836

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

680

AN:

3472

East Asian (EAS)

AF:

0.519

AC:

2669

AN:

5146

South Asian (SAS)

AF:

0.232

AC:

1117

AN:

4824

European-Finnish (FIN)

AF:

0.284

AC:

3002

AN:

10572

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15250

AN:

67962

Other (OTH)

AF:

0.253

AC:

535

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1450

2901

4351

5802

7252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.202

Hom.:

1672

Bravo

AF:

0.251

Asia WGS

AF:

0.349

AC:

1211

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.035

(source)

DANN

Benign

0.52

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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