rs10461985

Positions:

• chr5-37874307-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000503382.6(GDNF-AS1):​n.410+41G>A 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 151,508 control chromosomes in the GnomAD database, including 1,160 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 (1160 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GDNF-AS1 ENST00000503382.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521

Genes affected

GDNF-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDNF-AS1	NR_103441.2	n.410+41G>A		intron_variant
GDNF-AS1	NR_145476.1	n.429+41G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDNF-AS1	ENST00000503382.6	n.410+41G>A		intron_variant		1
GDNF-AS1	ENST00000510986.2	n.842+41G>A		intron_variant		1
GDNF-AS1	ENST00000514532.3	n.2719+41G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18192 AN: 151394 Hom.: 1158 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.105

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.120 AC: 18208 AN: 151508 Hom.: 1160 Cov.: 32 AF XY: 0.124 AC XY: 9164 AN XY: 73986

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0988 Hom.: 842

Bravo AF: 0.118

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10461985; hg19: chr5-37874409;