rs1042029

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-87934142-A-G
• chr14-87934142-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4	c.*590T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304	c.*590T>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_000153.4	ENSP00000261304.2
GALC	ENST00000544807.6	c.1744-143T>C		intron_variant	Intron 16 of 16	2		ENSP00000437513.2
GALC	ENST00000555000.5	n.1279-143T>C		intron_variant	Intron 11 of 13	2		ENSP00000450472.1
GALC	ENST00000393569.6	c.*590T>C		downstream_gene_variant		2		ENSP00000377199.2

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

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.533

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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.472

Alfa AF: 0.469 Hom.: 4858

Bravo AF: 0.462

Asia WGS AF: 0.563 AC: 1958 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs1042029; hg19: chr14-88400486;