rs17687109

chr14-87963346-A-G

Variant summary

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

The ENST00000622264.4(GALC):c.1190T>C(p.Leu397Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,595,282 control chromosomes in the GnomAD database, including 17,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1141 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16067 hom.)
• Consequence: GALC ENST00000622264.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0150

Genes affected

GALC (HGNC:4115): (galactosylceramidase) This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-87963346-A-G is Benign according to our data. Variant chr14-87963346-A-G is described in ClinVar as [Benign]. Clinvar id is 255369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALC	NM_000153.4	c.1161+38T>C		intron_variant		ENST00000261304.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000261304.7	c.1161+38T>C		intron_variant		1	NM_000153.4	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17183 AN: 152032 Hom.: 1138 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.126 AC: 31394 AN: 248394 Hom.: 2334 AF XY: 0.126 AC XY: 16980 AN XY: 134750

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.00201

Gnomad SAS exome AF: 0.0988

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.143 AC: 207088 AN: 1443132 Hom.: 16067 Cov.: 27 AF XY: 0.142 AC XY: 102468 AN XY: 719364

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.00164

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.113 AC: 17192 AN: 152150 Hom.: 1141 Cov.: 32 AF XY: 0.113 AC XY: 8434 AN XY: 74382

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0951

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.108

Alfa AF: 0.144 Hom.: 2314

Bravo AF: 0.107

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Galactosylceramide beta-galactosidase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	12
Dann	Benign	0.64

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: rs17687109; hg19: chr14-88429690; COSMIC: COSV54324625;