rs1012921

Variant names:

• chr14-87884832-G-A
• rs1012921
• ENST00000555000.5:n.*192+8524C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-87884832-G-A
• chr14-87884832-G-C
• chr14-87884832-G-T

Variant summary

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

The ENST00000555000.5(GALC):​n.*192+8524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,108 control chromosomes in the GnomAD database, including 44,886 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 0.77 (44886 hom., cov: 32)
• Consequence: GALC ENST00000555000.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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.*192+8524C>T		intron_variant	Intron 13 of 13	2		ENSP00000450472.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116426 AN: 151990 Hom.: 44844 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.766 AC: 116517 AN: 152108 Hom.: 44886 Cov.: 32 AF XY: 0.770 AC XY: 57283 AN XY: 74354

African (AFR) AF: 0.728 AC: 30183 AN: 41484

American (AMR) AF: 0.834 AC: 12757 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2911 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5090 AN: 5168

South Asian (SAS) AF: 0.866 AC: 4176 AN: 4824

European-Finnish (FIN) AF: 0.750 AC: 7935 AN: 10582

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50968 AN: 67972

Other (OTH) AF: 0.754 AC: 1595 AN: 2114

Alfa AF: 0.727 Hom.: 5650

Bravo AF: 0.771

Asia WGS AF: 0.908 AC: 3156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.70
DANN	Benign	0.43
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs1012921; hg19: chr14-88351176;