5-37817242-A-G

Variant names:

• chr5-37817242-A-G
• rs2973050
• NM_000514.4:c.152-1107T>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.152-1107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,110 control chromosomes in the GnomAD database, including 30,884 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 0.64 (30884 hom., cov: 33)
• Consequence: GDNF NM_000514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDNF	NM_000514.4	c.152-1107T>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.152-1107T>C		intron_variant	Intron 2 of 2	1	NM_000514.4	ENSP00000317145.2

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96712 AN: 151992 Hom.: 30845 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.636 AC: 96792 AN: 152110 Hom.: 30884 Cov.: 33 AF XY: 0.635 AC XY: 47199 AN XY: 74372

African (AFR) AF: 0.626 AC: 25942 AN: 41464

American (AMR) AF: 0.637 AC: 9738 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2142 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2865 AN: 5162

South Asian (SAS) AF: 0.594 AC: 2871 AN: 4830

European-Finnish (FIN) AF: 0.650 AC: 6885 AN: 10586

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44281 AN: 67998

Other (OTH) AF: 0.630 AC: 1332 AN: 2114

Alfa AF: 0.642 Hom.: 21145

Bravo AF: 0.634

Asia WGS AF: 0.564 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.44
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: rs2973050; hg19: chr5-37817344;