rs6996971

Positions:

• chr8-74380257-C-T

Variant summary

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

The ENST00000674710.1(GDAP1):​c.694+17204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,916 control chromosomes in the GnomAD database, including 19,829 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 0.51 (19829 hom., cov: 32)
• Consequence: GDAP1 ENST00000674710.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP1	NM_001362931.2	c.694+17204C>T		intron_variant			NP_001349860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000523640.2	c.165+28936C>T		intron_variant		3		ENSP00000502017
GDAP1	ENST00000524195.2	c.280+17204C>T		intron_variant		5		ENSP00000502308
GDAP1	ENST00000674710.1	c.694+17204C>T		intron_variant				ENSP00000502762

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77267 AN: 151796 Hom.: 19813 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.509 AC: 77329 AN: 151916 Hom.: 19829 Cov.: 32 AF XY: 0.507 AC XY: 37650 AN XY: 74220

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.477

Alfa AF: 0.478 Hom.: 35738

Bravo AF: 0.505

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6996971; hg19: chr8-75292492;