14-87941372-TAA-TAAAA

Position:

• chr14-87941372-TAA-TAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000153.4(GALC):​c.1834+22_1834+23insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 0)
  • Exomes 𝑓: 0.027 (7 hom.)
• Consequence: GALC NM_000153.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALC	NM_000153.4	c.1834+22_1834+23insTT		intron_variant		ENST00000261304.7	NP_000144.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALC	ENST00000261304.7	c.1834+22_1834+23insTT		intron_variant		1	NM_000153.4	ENSP00000261304	P1

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 351 AN: 146902 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00622

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00115

Gnomad ASJ AF: 0.00466

Gnomad EAS AF: 0.00240

Gnomad SAS AF: 0.000856

Gnomad FIN AF: 0.000744

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000690

Gnomad OTH AF: 0.00100

GnomAD4 exome AF: 0.0270 AC: 29834 AN: 1103342 Hom.: 7 Cov.: 16 AF XY: 0.0267 AC XY: 14908 AN XY: 558636

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0298

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.0523

Gnomad4 SAS exome AF: 0.0263

Gnomad4 FIN exome AF: 0.0209

Gnomad4 NFE exome AF: 0.0268

Gnomad4 OTH exome AF: 0.0276

GnomAD4 genome AF: 0.00243 AC: 357 AN: 146950 Hom.: 2 Cov.: 0 AF XY: 0.00252 AC XY: 180 AN XY: 71292

Gnomad4 AFR AF: 0.00631

Gnomad4 AMR AF: 0.00122

Gnomad4 ASJ AF: 0.00466

Gnomad4 EAS AF: 0.00240

Gnomad4 SAS AF: 0.000859

Gnomad4 FIN AF: 0.000744

Gnomad4 NFE AF: 0.000690

Gnomad4 OTH AF: 0.000994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34752717; hg19: chr14-88407716;