rs10504576

chr8-74354444-A-G

Variant summary

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

The NM_018972.4(GDAP1):c.310+2978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,100 control chromosomes in the GnomAD database, including 16,790 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 0.47 (16790 hom., cov: 33)
• Consequence: GDAP1 NM_018972.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

Genes affected

GDAP1 (HGNC:15968): (ganglioside induced differentiation associated protein 1) This gene encodes a member of the ganglioside-induced differentiation-associated protein family, which may play a role in a signal transduction pathway during neuronal development. Mutations in this gene have been associated with various forms of Charcot-Marie-Tooth Disease and neuropathy. Two transcript variants encoding different isoforms and a noncoding variant have been identified for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDAP1	NM_018972.4	c.310+2978A>G		intron_variant		ENST00000220822.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDAP1	ENST00000220822.12	c.310+2978A>G		intron_variant		1	NM_018972.4	P3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71417 AN: 151982 Hom.: 16783 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.470 AC: 71457 AN: 152100 Hom.: 16790 Cov.: 33 AF XY: 0.471 AC XY: 34994 AN XY: 74346

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.450

Alfa AF: 0.483 Hom.: 8043

Bravo AF: 0.460

Asia WGS AF: 0.459 AC: 1590 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	15
Dann	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs10504576; hg19: chr8-75266679; COSMIC: COSV55187151; COSMIC: COSV55187151;