rs7152233

Positions:

• chr14-87894832-G-A

Variant summary

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

The ENST00000555000.5(GALC):​c.*75-1359C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,918 control chromosomes in the GnomAD database, including 11,201 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 0.34 (11201 hom., cov: 32)
• Consequence: GALC ENST00000555000.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 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
GALC	ENST00000555000.5	c.*75-1359C>T		intron_variant, NMD_transcript_variant		2		ENSP00000450472

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51969 AN: 151800 Hom.: 11202 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.342 AC: 51962 AN: 151918 Hom.: 11201 Cov.: 32 AF XY: 0.339 AC XY: 25150 AN XY: 74250

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.375

Alfa AF: 0.442 Hom.: 7326

Bravo AF: 0.324

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7152233; hg19: chr14-88361176;