rs2289511

Positions:

• chr14-87988566-G-A

Variant summary

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

The NM_000153.4(GALC):​c.196-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,354,320 control chromosomes in the GnomAD database, including 243,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26971 hom., cov: 32)
  • Exomes 𝑓: 0.60 (216676 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.658

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=-0.93).
• BP6: Variant 14-87988566-G-A is Benign according to our data. Variant chr14-87988566-G-A is described in ClinVar as [Benign]. Clinvar id is 255374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALC	NM_000153.4	c.196-43C>T		intron_variant		ENST00000261304.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000261304.7	c.196-43C>T		intron_variant		1	NM_000153.4	P1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90205 AN: 151872 Hom.: 26963 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.590

GnomAD3 exomes AF: 0.622 AC: 152872 AN: 245826 Hom.: 48168 AF XY: 0.617 AC XY: 82574 AN XY: 133826

Gnomad AFR exome AF: 0.564

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.825

Gnomad SAS exome AF: 0.593

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.599 AC: 719780 AN: 1202330 Hom.: 216676 Cov.: 18 AF XY: 0.598 AC XY: 366070 AN XY: 611976

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.803

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.602

GnomAD4 genome AF: 0.594 AC: 90249 AN: 151990 Hom.: 26971 Cov.: 32 AF XY: 0.596 AC XY: 44246 AN XY: 74294

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.585

Alfa AF: 0.589 Hom.: 7926

Bravo AF: 0.604

Asia WGS AF: 0.615 AC: 2140 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	-0.93
CADD	Benign	2.6
DANN	Benign	0.61

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: rs2289511; hg19: chr14-88454910;