chr14-87934142-A-G

Variant names:

• chr14-87934142-A-G
• rs1042029
• NM_000153.4:c.*590T>C

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.*590T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,416,104 control chromosomes in the GnomAD database, including 199,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17937 hom., cov: 33)
  • Exomes 𝑓: 0.53 (181845 hom.)
• Consequence: GALC NM_000153.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.85
• Publications: 13 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, PanelApp Australia, Genomics England PanelApp, Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-87934142-A-G is Benign according to our data. Variant chr14-87934142-A-G is described in ClinVar as Benign. ClinVar VariationId is 314741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 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.*590T>C		3_prime_UTR	Exon 17 of 17	NP_000144.2	P54803-1
	GALC	NM_001201401.2		c.*590T>C		3_prime_UTR	Exon 16 of 16	NP_001188330.1	P54803-3
	GALC	NM_001201402.2		c.*590T>C		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.*590T>C		3_prime_UTR	Exon 17 of 17	ENSP00000261304.2	P54803-1
	GALC	ENST00000921945.1		c.*590T>C		3_prime_UTR	Exon 16 of 16	ENSP00000592004.1
	GALC	ENST00000950382.1		c.*590T>C		3_prime_UTR	Exon 17 of 17	ENSP00000620441.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70593 AN: 151946 Hom.: 17933 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.531 AC: 671746 AN: 1264040 Hom.: 181845 Cov.: 23 AF XY: 0.533 AC XY: 327899 AN XY: 614788

African (AFR) AF: 0.243 AC: 6698 AN: 27610

American (AMR) AF: 0.663 AC: 14717 AN: 22206

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 10191 AN: 19234

East Asian (EAS) AF: 0.758 AC: 26118 AN: 34478

South Asian (SAS) AF: 0.598 AC: 34538 AN: 57754

European-Finnish (FIN) AF: 0.547 AC: 15870 AN: 28992

Middle Eastern (MID) AF: 0.557 AC: 2143 AN: 3844

European-Non Finnish (NFE) AF: 0.524 AC: 533469 AN: 1017422

Other (OTH) AF: 0.533 AC: 28002 AN: 52500

GnomAD4 genome AF: 0.464 AC: 70610 AN: 152064 Hom.: 17937 Cov.: 33 AF XY: 0.470 AC XY: 34939 AN XY: 74330

African (AFR) AF: 0.257 AC: 10688 AN: 41512

American (AMR) AF: 0.587 AC: 8948 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3468

East Asian (EAS) AF: 0.751 AC: 3879 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2753 AN: 4826

European-Finnish (FIN) AF: 0.523 AC: 5525 AN: 10568

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

European-Non Finnish (NFE) AF: 0.522 AC: 35449 AN: 67972

Other (OTH) AF: 0.472 AC: 997 AN: 2112

Alfa AF: 0.476 Hom.: 8192

Bravo AF: 0.462

Asia WGS AF: 0.563 AC: 1958 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.86
PhyloP100		1.8
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: rs1042029; hg19: chr14-88400486;