chr14-87941573-G-A

Variant names:

• chr14-87941573-G-A
• rs12432149
• NM_000153.4:c.1671-15C>T

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.1671-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,498,288 control chromosomes in the GnomAD database, including 210,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17740 hom., cov: 32)
  • Exomes 𝑓: 0.53 (192280 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.03
• Publications: 18 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=-0.9).
• BP6: Variant 14-87941573-G-A is Benign according to our data. Variant chr14-87941573-G-A is described in ClinVar as Benign. ClinVar VariationId is 92496.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.1671-15C>T		intron	N/A	NP_000144.2	P54803-1
	GALC	NM_001201401.2		c.1602-15C>T		intron	N/A	NP_001188330.1	P54803-3
	GALC	NM_001201402.2		c.1593-15C>T		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.1671-15C>T		intron	N/A	ENSP00000261304.2	P54803-1
	GALC	ENST00000921945.1		c.1632-15C>T		intron	N/A	ENSP00000592004.1
	GALC	ENST00000950382.1		c.1605-15C>T		intron	N/A	ENSP00000620441.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69840 AN: 151698 Hom.: 17739 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.472

GnomAD2 exomes AF: 0.551 AC: 136630 AN: 248100 AF XY: 0.552

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.764

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.529 AC: 712053 AN: 1346472 Hom.: 192280 Cov.: 23 AF XY: 0.531 AC XY: 358949 AN XY: 676576

African (AFR) AF: 0.221 AC: 6994 AN: 31624

American (AMR) AF: 0.664 AC: 29508 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 13023 AN: 25330

East Asian (EAS) AF: 0.757 AC: 29541 AN: 39002

South Asian (SAS) AF: 0.579 AC: 48467 AN: 83694

European-Finnish (FIN) AF: 0.530 AC: 28228 AN: 53216

Middle Eastern (MID) AF: 0.550 AC: 3046 AN: 5536

European-Non Finnish (NFE) AF: 0.520 AC: 523465 AN: 1007192

Other (OTH) AF: 0.528 AC: 29781 AN: 56446

GnomAD4 genome AF: 0.460 AC: 69846 AN: 151816 Hom.: 17740 Cov.: 32 AF XY: 0.466 AC XY: 34566 AN XY: 74210

African (AFR) AF: 0.242 AC: 10038 AN: 41428

American (AMR) AF: 0.586 AC: 8922 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.751 AC: 3845 AN: 5118

South Asian (SAS) AF: 0.570 AC: 2750 AN: 4822

European-Finnish (FIN) AF: 0.525 AC: 5547 AN: 10572

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

European-Non Finnish (NFE) AF: 0.521 AC: 35385 AN: 67858

Other (OTH) AF: 0.468 AC: 988 AN: 2110

Alfa AF: 0.492 Hom.: 3781

Bravo AF: 0.456

Asia WGS AF: 0.560 AC: 1948 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Galactosylceramide beta-galactosidase deficiency (4)
-	-	4	not specified (4)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.024
DANN	Benign	0.26
PhyloP100		-2.0
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: rs12432149; hg19: chr14-88407917;