rs1012921

Positions:

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

Variant summary

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

The ENST00000555000.5(GALC):​c.*192+8524C>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 0.766 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

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=-0.96).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALC	ENST00000555000.5	c.*192+8524C>T		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.754

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1012921; hg19: chr14-88351176;