8-74382875-G-C

Variant names:

• chr8-74382875-G-C
• rs4469448
• ENST00000674710.1:c.694+19822G>C

Variant summary

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

The NM_001362931.2(GDAP1):​c.694+19822G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,774 control chromosomes in the GnomAD database, including 17,966 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 0.49 (17966 hom., cov: 31)
• Consequence: GDAP1 NM_001362931.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1	NM_001362931.2	c.694+19822G>C		intron_variant	Intron 5 of 5		NP_001349860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000674710.1	c.694+19822G>C		intron_variant	Intron 5 of 7			ENSP00000502762.1
GDAP1	ENST00000675999.1	c.694+19822G>C		intron_variant	Intron 5 of 5			ENSP00000502572.1
GDAP1	ENST00000676207.1	c.694+19822G>C		intron_variant	Intron 5 of 5			ENSP00000502638.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73720 AN: 151656 Hom.: 17947 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.486 AC: 73779 AN: 151774 Hom.: 17966 Cov.: 31 AF XY: 0.486 AC XY: 36050 AN XY: 74142

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.462

Alfa AF: 0.477 Hom.: 2099

Bravo AF: 0.481

Asia WGS AF: 0.459 AC: 1590 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.37
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4469448; hg19: chr8-75295110;