rs11300320

Variant names:

• chr14-87950751-GAA-G
• rs11300320
• NM_000153.4:c.1162-5_1162-4delTT

Your query was ambiguous. Multiple possible variants found:

• chr14-87950751-GAA-G
• chr14-87950751-GAA-GA
• chr14-87950751-GAA-GAAA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000153.4(GALC):​c.1162-5_1162-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000752 in 1,277,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00085 (0 hom.)
• Consequence: GALC NM_000153.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.817
• Publications: 7 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, Myriad Women’s Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 14-87950751-GAA-G is Benign according to our data. Variant chr14-87950751-GAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 752088.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4	c.1162-5_1162-4delTT		splice_region_variant, intron_variant	Intron 10 of 16	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7	c.1162-5_1162-4delTT		splice_region_variant, intron_variant	Intron 10 of 16	1	NM_000153.4	ENSP00000261304.2

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149412 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000579 AC: 123 AN: 212618 AF XY: 0.000666

Gnomad AFR exome AF: 0.000299

Gnomad AMR exome AF: 0.000422

Gnomad ASJ exome AF: 0.000225

Gnomad EAS exome AF: 0.000532

Gnomad FIN exome AF: 0.0000995

Gnomad NFE exome AF: 0.000603

Gnomad OTH exome AF: 0.000592

GnomAD4 exome AF: 0.000851 AC: 960 AN: 1128574 Hom.: 0 AF XY: 0.000845 AC XY: 481 AN XY: 568936

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000584 AC: 16 AN: 27408

American (AMR) AF: 0.000471 AC: 18 AN: 38246

Ashkenazi Jewish (ASJ) AF: 0.000369 AC: 8 AN: 21656

East Asian (EAS) AF: 0.000266 AC: 9 AN: 33782

South Asian (SAS) AF: 0.000902 AC: 63 AN: 69818

European-Finnish (FIN) AF: 0.000189 AC: 9 AN: 47558

Middle Eastern (MID) AF: 0.000208 AC: 1 AN: 4810

European-Non Finnish (NFE) AF: 0.000954 AC: 799 AN: 837868

Other (OTH) AF: 0.000780 AC: 37 AN: 47428

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149412 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72702

African (AFR) AF: 0.0000246 AC: 1 AN: 40644

American (AMR) AF: 0.00 AC: 0 AN: 14894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67296

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00398 Hom.: 6173

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Galactosylceramide beta-galactosidase deficiency Benign:1

Apr 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.82
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11300320; hg19: chr14-88417095;