14-87941372-TAAA-TAAAA

Variant names:

• chr14-87941372-T-TA
• rs34752717
• NM_000153.4:c.1834+22dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000153.4(GALC):​c.1834+22dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16927 hom., cov: 0)
  • Exomes 𝑓: 0.43 (21847 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.263
• Publications: 2 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-87941372-T-TA is Benign according to our data. Variant chr14-87941372-T-TA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALC	NM_000153.4	c.1834+22dupT		intron_variant	Intron 15 of 16	ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7	c.1834+22_1834+23insT		intron_variant	Intron 15 of 16	1	NM_000153.4	ENSP00000261304.2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 67804 AN: 146810 Hom.: 16934 Cov.: 0

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.536

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.477

GnomAD2 exomes AF: 0.461 AC: 77293 AN: 167536 AF XY: 0.462

Gnomad AFR exome AF: 0.326

Gnomad AMR exome AF: 0.491

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.499

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.463

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.431 AC: 472655 AN: 1095866 Hom.: 21847 Cov.: 16 AF XY: 0.431 AC XY: 239134 AN XY: 554492

African (AFR) AF: 0.268 AC: 6288 AN: 23472

American (AMR) AF: 0.461 AC: 16721 AN: 36280

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 8873 AN: 21128

East Asian (EAS) AF: 0.493 AC: 16975 AN: 34434

South Asian (SAS) AF: 0.436 AC: 30881 AN: 70908

European-Finnish (FIN) AF: 0.421 AC: 17387 AN: 41340

Middle Eastern (MID) AF: 0.460 AC: 2147 AN: 4672

European-Non Finnish (NFE) AF: 0.432 AC: 353431 AN: 817288

Other (OTH) AF: 0.431 AC: 19952 AN: 46344

GnomAD4 genome AF: 0.462 AC: 67791 AN: 146856 Hom.: 16927 Cov.: 0 AF XY: 0.467 AC XY: 33305 AN XY: 71242

African (AFR) AF: 0.248 AC: 9851 AN: 39790

American (AMR) AF: 0.586 AC: 8636 AN: 14746

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1716 AN: 3428

East Asian (EAS) AF: 0.747 AC: 3733 AN: 4996

South Asian (SAS) AF: 0.584 AC: 2714 AN: 4648

European-Finnish (FIN) AF: 0.520 AC: 4893 AN: 9408

Middle Eastern (MID) AF: 0.532 AC: 151 AN: 284

European-Non Finnish (NFE) AF: 0.521 AC: 34690 AN: 66640

Other (OTH) AF: 0.475 AC: 955 AN: 2012

Alfa AF: 0.326 Hom.: 978

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Jun 12, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26
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: rs34752717; hg19: chr14-88407716;