chr10-49371035-C-G

Variant names:

• chr10-49371035-C-G
• rs11101115
• NM_001276451.2:c.527-4654G>C

Variant summary

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

The NM_001276451.2(DRGX):​c.527-4654G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,244 control chromosomes in the GnomAD database, including 945 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 0.098 (945 hom., cov: 32)
• Consequence: DRGX NM_001276451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRGX	NM_001276451.2	c.527-4654G>C		intron_variant	Intron 6 of 6	ENST00000374139.8	NP_001263380.1
DRGX	XM_011540089.4	c.632-4654G>C		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	c.527-4654G>C		intron_variant	Intron 6 of 6	2	NM_001276451.2	ENSP00000363254.1

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14962 AN: 152124 Hom.: 946 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0808

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

GnomAD4 genome AF: 0.0983 AC: 14962 AN: 152244 Hom.: 945 Cov.: 32 AF XY: 0.102 AC XY: 7608 AN XY: 74416

African (AFR) AF: 0.0323 AC: 1343 AN: 41562

American (AMR) AF: 0.140 AC: 2148 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3472

East Asian (EAS) AF: 0.104 AC: 538 AN: 5172

South Asian (SAS) AF: 0.0722 AC: 348 AN: 4818

European-Finnish (FIN) AF: 0.174 AC: 1837 AN: 10584

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8278 AN: 68016

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.114 Hom.: 131

Bravo AF: 0.0937

Asia WGS AF: 0.0870 AC: 303 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	0.19
DANN	Benign	0.52
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs11101115; hg19: chr10-50579080;