rs141199615

Variant names:

• chr14-87933543-TATC-T
• rs141199615
• NM_000153.4:c.*1186_*1188delGAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000153.4(GALC):​c.*1186_*1188delGAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 155,638 control chromosomes in the GnomAD database, including 18,478 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17813 hom., cov: 0)
  • Exomes 𝑓: 0.58 (665 hom.)
• Consequence: GALC NM_000153.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 14-87933543-TATC-T is Benign according to our data. Variant chr14-87933543-TATC-T is described in ClinVar as Benign. ClinVar VariationId is 314732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 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.*1186_*1188delGAT		3_prime_UTR	Exon 17 of 17	NP_000144.2	P54803-1
	GALC	NM_001201401.2		c.*1186_*1188delGAT		3_prime_UTR	Exon 16 of 16	NP_001188330.1	P54803-3
	GALC	NM_001201402.2		c.*1186_*1188delGAT		3_prime_UTR	Exon 17 of 17	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.*1186_*1188delGAT		3_prime_UTR	Exon 17 of 17	ENSP00000261304.2	P54803-1
	GALC	ENST00000921945.1		c.*1186_*1188delGAT		3_prime_UTR	Exon 16 of 16	ENSP00000592004.1
	GALC	ENST00000950382.1		c.*1186_*1188delGAT		3_prime_UTR	Exon 17 of 17	ENSP00000620441.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70340 AN: 151632 Hom.: 17809 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.575 AC: 2237 AN: 3888 Hom.: 665 AF XY: 0.578 AC XY: 1154 AN XY: 1998

African (AFR) AF: 0.333 AC: 56 AN: 168

American (AMR) AF: 0.698 AC: 88 AN: 126

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 75 AN: 150

East Asian (EAS) AF: 0.718 AC: 227 AN: 316

South Asian (SAS) AF: 0.500 AC: 22 AN: 44

European-Finnish (FIN) AF: 0.548 AC: 136 AN: 248

Middle Eastern (MID) AF: 0.583 AC: 7 AN: 12

European-Non Finnish (NFE) AF: 0.574 AC: 1495 AN: 2606

Other (OTH) AF: 0.601 AC: 131 AN: 218

GnomAD4 genome AF: 0.464 AC: 70357 AN: 151750 Hom.: 17813 Cov.: 0 AF XY: 0.469 AC XY: 34796 AN XY: 74146

African (AFR) AF: 0.257 AC: 10642 AN: 41450

American (AMR) AF: 0.587 AC: 8935 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3839 AN: 5116

South Asian (SAS) AF: 0.570 AC: 2749 AN: 4824

European-Finnish (FIN) AF: 0.521 AC: 5479 AN: 10510

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35346 AN: 67836

Other (OTH) AF: 0.472 AC: 995 AN: 2106

Alfa AF: 0.495 Hom.: 2409

Bravo AF: 0.461

Asia WGS AF: 0.561 AC: 1942 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Galactosylceramide beta-galactosidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

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: rs141199615; hg19: chr14-88399887; COSMIC: COSV54323828; COSMIC: COSV54323828;