chr8-74350331-A-T

Position:

• chr8-74350331-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000675944.1(GDAP1):​c.-122A>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00558 in 719,546 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (66 hom., cov: 34)
  • Exomes 𝑓: 0.0024 (34 hom.)
• Consequence: GDAP1 ENST00000675944.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.92

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 8-74350331-A-T is Benign according to our data. Variant chr8-74350331-A-T is described in ClinVar as [Benign]. Clinvar id is 1244430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

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.-100A>T		5_prime_UTR_variant	1/6			ENSP00000502637
GDAP1	ENST00000675944.1	c.-122A>T		5_prime_UTR_variant	1/6			ENSP00000502673
GDAP1	ENST00000674612.1	c.-17-9806A>T		intron_variant				ENSP00000501864

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2664 AN: 151878 Hom.: 65 Cov.: 34

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00236 AC: 1340 AN: 567556 Hom.: 34 AF XY: 0.00199 AC XY: 609 AN XY: 306240

Gnomad4 AFR exome AF: 0.0591

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000798

Gnomad4 FIN exome AF: 0.0000291

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00460

GnomAD4 genome AF: 0.0176 AC: 2677 AN: 151990 Hom.: 66 Cov.: 34 AF XY: 0.0169 AC XY: 1254 AN XY: 74290

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.00824

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0131 Hom.: 2

Bravo AF: 0.0204

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs146798895; hg19: chr8-75262566;