8-74355383-A-G

Position:

• chr8-74355383-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+3917A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,086 control chromosomes in the GnomAD database, including 14,367 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 0.43 (14367 hom., cov: 33)
• Consequence: GDAP1 NM_018972.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP1	NM_018972.4	c.310+3917A>G		intron_variant		ENST00000220822.12	NP_061845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000220822.12	c.310+3917A>G		intron_variant		1	NM_018972.4	ENSP00000220822	P3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65584 AN: 151968 Hom.: 14366 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.431 AC: 65610 AN: 152086 Hom.: 14367 Cov.: 33 AF XY: 0.434 AC XY: 32233 AN XY: 74342

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.420

Alfa AF: 0.455 Hom.: 1993

Bravo AF: 0.419

Asia WGS AF: 0.453 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.71

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: rs9298238; hg19: chr8-75267618;