rs2910705

Variant names:

• chr5-37822143-T-C
• rs2910705
• NM_000514.4:c.152-6008A>G

Variant summary

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

The NM_000514.4(GDNF):​c.152-6008A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,064 control chromosomes in the GnomAD database, including 1,333 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 0.12 (1333 hom., cov: 32)
• Consequence: GDNF NM_000514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 3 publications found

Genes affected

GDNF (HGNC:4232): (glial cell derived neurotrophic factor) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The recombinant form of this protein, a highly conserved neurotrophic factor, was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. This protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Mutations in this gene may be associated with Hirschsprung disease and Tourette syndrome. This gene encodes multiple protein isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

GDNF-AS1 (HGNC:43592): (GDNF antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDNF	NM_000514.4	c.152-6008A>G		intron_variant	Intron 2 of 2	ENST00000326524.7	NP_000505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDNF	ENST00000326524.7	c.152-6008A>G		intron_variant	Intron 2 of 2	1	NM_000514.4	ENSP00000317145.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 151946 Hom.: 1330 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.120 AC: 18292 AN: 152064 Hom.: 1333 Cov.: 32 AF XY: 0.125 AC XY: 9305 AN XY: 74320

African (AFR) AF: 0.116 AC: 4803 AN: 41492

American (AMR) AF: 0.216 AC: 3299 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5148

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4808

European-Finnish (FIN) AF: 0.117 AC: 1239 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5973 AN: 67972

Other (OTH) AF: 0.110 AC: 232 AN: 2106

Alfa AF: 0.106 Hom.: 118

Bravo AF: 0.128

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.3
DANN	Benign	0.55
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2910705; hg19: chr5-37822245;