8-74350137-A-T

Position:

• chr8-74350137-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000675944.1(GDAP1):​c.-316A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 376,594 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (2 hom.)
• Consequence: GDAP1 ENST00000675944.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.366

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-74350137-A-T is Benign according to our data. Variant chr8-74350137-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1216335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00472 (718/151974) while in subpopulation AFR AF= 0.015 (624/41466). AF 95% confidence interval is 0.0141. There are 6 homozygotes in gnomad4. There are 333 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000674806.1	c.-294A>T		5_prime_UTR_variant	1/6			ENSP00000502637
GDAP1	ENST00000675944.1	c.-316A>T		5_prime_UTR_variant	1/6			ENSP00000502673
GDAP1	ENST00000674612.1	c.-17-10000A>T		intron_variant				ENSP00000501864

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 711 AN: 151860 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.00446

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.000654 AC: 147 AN: 224620 Hom.: 2 AF XY: 0.000574 AC XY: 69 AN XY: 120230

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.00220

Gnomad4 ASJ exome AF: 0.000803

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000547

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000757

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00472 AC: 718 AN: 151974 Hom.: 6 Cov.: 32 AF XY: 0.00448 AC XY: 333 AN XY: 74286

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00561

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.15
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112493177; hg19: chr8-75262372;