rs11101115

chr10-49371035-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DRGX	NM_001276451.2	c.527-4654G>C		intron_variant		ENST00000374139.8
DRGX	XM_011540089.4	c.632-4654G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRGX	ENST00000374139.8	c.527-4654G>C		intron_variant		2	NM_001276451.2	P1

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

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0722

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0799

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11101115; hg19: chr10-50579080;