rs2245387

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000153.4(GALC):​c.264+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,234,444 control chromosomes in the GnomAD database, including 84,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8509 hom., cov: 32)
  • Exomes 𝑓: 0.37 (76278 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.284
• Publications: 8 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: Laboratory for Molecular Medicine, Genomics England PanelApp, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-87988347-C-T is Benign according to our data. Variant chr14-87988347-C-T is described in ClinVar as Benign. ClinVar VariationId is 1177535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	NM_000153.4	MANE Select	c.264+108G>A		intron	N/A	NP_000144.2	P54803-1
	GALC	NM_001201401.2		c.196-140G>A		intron	N/A	NP_001188330.1	P54803-3
	GALC	NM_001201402.2		c.186+108G>A		intron	N/A	NP_001188331.1	P54803-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALC	ENST00000261304.7	TSL:1 MANE Select	c.264+108G>A		intron	N/A	ENSP00000261304.2	P54803-1
	GALC	ENST00000622264.4	TSL:1	c.252+108G>A		intron	N/A	ENSP00000480649.1	A0A087WX10
	GALC	ENST00000474294.6	TSL:1	n.254+108G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47140 AN: 151848 Hom.: 8509 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.366 AC: 395820 AN: 1082478 Hom.: 76278 Cov.: 14 AF XY: 0.368 AC XY: 203666 AN XY: 553352

African (AFR) AF: 0.122 AC: 3148 AN: 25870

American (AMR) AF: 0.508 AC: 21244 AN: 41860

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 8817 AN: 23366

East Asian (EAS) AF: 0.613 AC: 23124 AN: 37722

South Asian (SAS) AF: 0.431 AC: 33123 AN: 76880

European-Finnish (FIN) AF: 0.343 AC: 17944 AN: 52326

Middle Eastern (MID) AF: 0.372 AC: 1722 AN: 4632

European-Non Finnish (NFE) AF: 0.349 AC: 269620 AN: 772128

Other (OTH) AF: 0.358 AC: 17078 AN: 47694

GnomAD4 genome AF: 0.310 AC: 47141 AN: 151966 Hom.: 8509 Cov.: 32 AF XY: 0.316 AC XY: 23502 AN XY: 74274

African (AFR) AF: 0.133 AC: 5515 AN: 41458

American (AMR) AF: 0.439 AC: 6698 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1286 AN: 3472

East Asian (EAS) AF: 0.582 AC: 3006 AN: 5164

South Asian (SAS) AF: 0.415 AC: 2002 AN: 4828

European-Finnish (FIN) AF: 0.346 AC: 3647 AN: 10526

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23874 AN: 67938

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.316 Hom.: 1060

Bravo AF: 0.313

Asia WGS AF: 0.409 AC: 1425 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Galactosylceramide beta-galactosidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV54330103; COSMIC: COSV54330103;