rs1549250

Variant names:

• chr5-37821119-C-A
• rs1549250
• NM_000514.4:c.152-4984G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37821119-C-A
• chr5-37821119-C-T

Variant summary

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

The NM_000514.4(GDNF):​c.152-4984G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,910 control chromosomes in the GnomAD database, including 23,686 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 0.55 (23686 hom., cov: 31)
• Consequence: GDNF NM_000514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 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.152-4984G>T		intron	N/A	NP_000505.1	P39905-1
	GDNF	NM_001190468.1		c.203-4984G>T		intron	N/A	NP_001177397.1	P39905-3
	GDNF	NM_001190469.1		c.125-4984G>T		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.152-4984G>T		intron	N/A	ENSP00000317145.2	P39905-1
	GDNF	ENST00000427982.5	TSL:1	c.203-4984G>T		intron	N/A	ENSP00000409007.1	P39905-3
	GDNF	ENST00000381826.8	TSL:1	c.125-4984G>T		intron	N/A	ENSP00000371248.4	P39905-4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83887 AN: 151792 Hom.: 23658 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.553 AC: 83956 AN: 151910 Hom.: 23686 Cov.: 31 AF XY: 0.545 AC XY: 40469 AN XY: 74224

African (AFR) AF: 0.602 AC: 24926 AN: 41402

American (AMR) AF: 0.440 AC: 6714 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1890 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1716 AN: 5156

South Asian (SAS) AF: 0.411 AC: 1979 AN: 4810

European-Finnish (FIN) AF: 0.538 AC: 5666 AN: 10536

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39344 AN: 67968

Other (OTH) AF: 0.546 AC: 1152 AN: 2108

Alfa AF: 0.557 Hom.: 39642

Bravo AF: 0.546

Asia WGS AF: 0.361 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.58
PhyloP100		-0.21
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: rs1549250; hg19: chr5-37821221;