Genetic Variant GALC:c.264+108G>A (chr14-87988347-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.284

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4 link	c.264+108G>A		intron_variant	Intron 2 of 16	ENST00000261304.7	NP_000144.2	P54803-1A0A0A0MQV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7 link	c.264+108G>A		intron_variant	Intron 2 of 16	1	NM_000153.4	ENSP00000261304.2		P54803-1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47140

AN:

151848

Hom.:

8509

Cov.:

show subpopulations

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.:

AF XY:

0.368

AC XY:

203666

AN XY:

553352

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.377

Gnomad4 EAS exome

AF:

0.613

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.310

AC:

47141

AN:

151966

Hom.:

8509

Cov.:

AF XY:

0.316

AC XY:

23502

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.582

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.323

Hom.:

1051

Bravo

AF:

0.313

Asia WGS

AF:

0.409

AC:

1425

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Galactosylceramide beta-galactosidase deficiency

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.6

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over