20-44268909-T-G

Position:

• chr20-44268909-T-G

Variant summary

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

The ENST00000342560.10(GDAP1L1):​c.760+4350T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,038 control chromosomes in the GnomAD database, including 8,002 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 0.31 (8002 hom., cov: 32)
• Consequence: GDAP1L1 ENST00000342560.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

GDAP1L1 (HGNC:4213): (ganglioside induced differentiation associated protein 1 like 1) The ganglioside GD3 synthase causes cell differentiation with neurite sprouting when transfected into the mouse neuroblastoma cell line Neuro2a. After differentiation, the expression of several genes is upregulated, including one that encodes a protein termed ganglioside-induced differentiation-associated protein 1 (Gdap1). A similar gene was found in humans, and mutations in the human gene are associated with Charcot-Marie-Tooth type 4A disease. The protein encoded by this gene is similar in sequence to the human GDAP1 protein. Several transcript variants encoding different isoforms, as well as a noncoding transcript variant, have been found 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP1L1	NM_024034.6	c.760+4350T>G		intron_variant		ENST00000342560.10	NP_076939.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1L1	ENST00000342560.10	c.760+4350T>G		intron_variant		1	NM_024034.6	ENSP00000341782	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46474 AN: 151920 Hom.: 7976 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.306 AC: 46551 AN: 152038 Hom.: 8002 Cov.: 32 AF XY: 0.313 AC XY: 23295 AN XY: 74338

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.324

Alfa AF: 0.213 Hom.: 705

Bravo AF: 0.325

Asia WGS AF: 0.427 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.72

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: rs6031492; hg19: chr20-42897549;