rs2245387

Variant names:

• chr14-87988347-C-A
• rs2245387
• NM_000153.4:c.264+108G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-87988347-C-A
• chr14-87988347-C-G
• chr14-87988347-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000153.4(GALC):​c.264+108G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000922 in 1,084,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000153.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	NM_000153.4	MANE Select	c.264+108G>T		intron	N/A	NP_000144.2
	GALC	NM_001201401.2		c.196-140G>T		intron	N/A	NP_001188330.1
	GALC	NM_001201402.2		c.186+108G>T		intron	N/A	NP_001188331.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	ENST00000261304.7	TSL:1 MANE Select	c.264+108G>T		intron	N/A	ENSP00000261304.2
	GALC	ENST00000622264.4	TSL:1	c.252+108G>T		intron	N/A	ENSP00000480649.1
	GALC	ENST00000474294.6	TSL:1	n.254+108G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.22e-7 AC: 1 AN: 1084556 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 554300

African (AFR) AF: 0.00 AC: 0 AN: 25900

American (AMR) AF: 0.00 AC: 0 AN: 41906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23378

East Asian (EAS) AF: 0.00 AC: 0 AN: 37762

South Asian (SAS) AF: 0.00 AC: 0 AN: 76950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4636

European-Non Finnish (NFE) AF: 0.00000129 AC: 1 AN: 773926

Other (OTH) AF: 0.00 AC: 0 AN: 47752

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		-0.28

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

Other links and lift over

dbSNP: rs2245387; hg19: chr14-88454691;