5-37828202-C-T

Variant names:

• chr5-37828202-C-T
• rs2910702
• NM_000514.4:c.151+6444G>A

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+6444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,138 control chromosomes in the GnomAD database, including 42,002 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 0.74 (42002 hom., cov: 32)
• Consequence: GDNF NM_000514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDNF	NM_000514.4	MANE Select	c.151+6444G>A		intron	N/A	NP_000505.1	P39905-1
	GDNF	NM_001190468.1		c.202+6444G>A		intron	N/A	NP_001177397.1	P39905-3
	GDNF	NM_001190469.1		c.124+6522G>A		intron	N/A	NP_001177398.1	P39905-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDNF	ENST00000326524.7	TSL:1 MANE Select	c.151+6444G>A		intron	N/A	ENSP00000317145.2	P39905-1
	GDNF	ENST00000427982.5	TSL:1	c.202+6444G>A		intron	N/A	ENSP00000409007.1	P39905-3
	GDNF	ENST00000381826.8	TSL:1	c.124+6522G>A		intron	N/A	ENSP00000371248.4	P39905-4

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112924 AN: 152020 Hom.: 41961 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.743 AC: 113013 AN: 152138 Hom.: 42002 Cov.: 32 AF XY: 0.745 AC XY: 55406 AN XY: 74380

African (AFR) AF: 0.725 AC: 30089 AN: 41492

American (AMR) AF: 0.767 AC: 11730 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3416 AN: 5168

South Asian (SAS) AF: 0.805 AC: 3881 AN: 4822

European-Finnish (FIN) AF: 0.782 AC: 8280 AN: 10588

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50708 AN: 67988

Other (OTH) AF: 0.720 AC: 1520 AN: 2112

Alfa AF: 0.740 Hom.: 5838

Bravo AF: 0.737

Asia WGS AF: 0.742 AC: 2583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.45
PhyloP100		-0.65
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: rs2910702; hg19: chr5-37828304;