14-87945029-A-G

Position:

• chr14-87945029-A-G

Variant summary

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

The NM_000153.4(GALC):​c.1670+524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,888 control chromosomes in the GnomAD database, including 16,203 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 0.46 (16203 hom., cov: 32)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4	c.1670+524T>C		intron_variant		ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7	c.1670+524T>C		intron_variant		1	NM_000153.4	ENSP00000261304	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69444 AN: 151770 Hom.: 16185 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.458 AC: 69497 AN: 151888 Hom.: 16203 Cov.: 32 AF XY: 0.453 AC XY: 33654 AN XY: 74232

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.466

Alfa AF: 0.462 Hom.: 2925

Bravo AF: 0.450

Asia WGS AF: 0.397 AC: 1380 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.8
DANN	Benign	0.84

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: rs429923; hg19: chr14-88411373;