NM_001276451.2:c.234+1465G>T

Variant names:

• chr10-49388668-C-A
• rs17010003
• NM_001276451.2:c.234+1465G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001276451.2(DRGX):​c.234+1465G>T variant causes a intron change. The variant allele was found at a frequency of 0.0406 in 152,330 control chromosomes in the GnomAD database, including 170 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 0.041 (170 hom., cov: 33)
• Consequence: DRGX NM_001276451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0406 (6192/152330) while in subpopulation AFR AF = 0.0513 (2131/41576). AF 95% confidence interval is 0.0494. There are 170 homozygotes in GnomAd4. There are 3227 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 170 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276451.2. 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
	DRGX	NM_001276451.2	MANE Select	c.234+1465G>T		intron	N/A	NP_001263380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRGX	ENST00000374139.8	TSL:2 MANE Select	c.234+1465G>T		intron	N/A	ENSP00000363254.1

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6182 AN: 152212 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0335

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

GnomAD4 genome AF: 0.0406 AC: 6192 AN: 152330 Hom.: 170 Cov.: 33 AF XY: 0.0433 AC XY: 3227 AN XY: 74488

African (AFR) AF: 0.0513 AC: 2131 AN: 41576

American (AMR) AF: 0.0229 AC: 350 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1207 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0332 AC: 2259 AN: 68038

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0369 Hom.: 26

Bravo AF: 0.0350

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.86
PhyloP100		5.8
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17010003; hg19: chr10-50596714;