NM_000514.4:c.151+7523G>C

Variant names:

• chr5-37827123-C-G
• rs2910704
• NM_000514.4:c.151+7523G>C

Variant summary

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

The NM_000514.4(GDNF):​c.151+7523G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 150,760 control chromosomes in the GnomAD database, including 9,424 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 0.35 (9424 hom., cov: 31)
• Consequence: GDNF NM_000514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDNF	NM_000514.4	c.151+7523G>C		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.151+7523G>C		intron_variant	Intron 2 of 2	1	NM_000514.4	ENSP00000317145.2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52734 AN: 150644 Hom.: 9412 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.350 AC: 52785 AN: 150760 Hom.: 9424 Cov.: 31 AF XY: 0.356 AC XY: 26178 AN XY: 73518

African (AFR) AF: 0.371 AC: 15185 AN: 40982

American (AMR) AF: 0.429 AC: 6504 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1155 AN: 3454

East Asian (EAS) AF: 0.330 AC: 1689 AN: 5118

South Asian (SAS) AF: 0.459 AC: 2188 AN: 4772

European-Finnish (FIN) AF: 0.378 AC: 3863 AN: 10212

Middle Eastern (MID) AF: 0.245 AC: 70 AN: 286

European-Non Finnish (NFE) AF: 0.312 AC: 21171 AN: 67776

Other (OTH) AF: 0.304 AC: 636 AN: 2094

Alfa AF: 0.182 Hom.: 357

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.16
PhyloP100		0.15
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: rs2910704; hg19: chr5-37827225;