rs7152233

Variant names:

• chr14-87894832-G-A
• rs7152233
• ENST00000555000.5:n.*75-1359C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555000.5(GALC):​n.*75-1359C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 4 publications found

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]

GALC Gene-Disease associations (from GenCC):

• Krabbe disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Myriad Women’s Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000555000.5	n.*75-1359C>T		intron_variant	Intron 12 of 13	2		ENSP00000450472.1

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

African (AFR) AF: 0.114 AC: 4724 AN: 41420

American (AMR) AF: 0.298 AC: 4544 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3470

East Asian (EAS) AF: 0.0632 AC: 327 AN: 5176

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4818

European-Finnish (FIN) AF: 0.455 AC: 4794 AN: 10536

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32709 AN: 67926

Other (OTH) AF: 0.375 AC: 793 AN: 2112

Alfa AF: 0.445 Hom.: 8221

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
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs7152233; hg19: chr14-88361176;