1-23847603-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000147.5(FUCA1):c.1160+1046A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,054 control chromosomes in the GnomAD database, including 10,695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10695 hom., cov: 32)
• Consequence: FUCA1 NM_000147.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

FUCA1 (HGNC:4006): (alpha-L-fucosidase 1) The protein encoded by this gene is a lysosomal enzyme involved in the degradation of fucose-containing glycoproteins and glycolipids. Mutations in this gene are associated with fucosidosis (FUCA1D), which is an autosomal recessive lysosomal storage disease. A pseudogene of this locus is present on chr 2.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUCA1	NM_000147.5	c.1160+1046A>C		intron_variant		ENST00000374479.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUCA1	ENST00000374479.4	c.1160+1046A>C		intron_variant		1	NM_000147.5	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55549 AN: 151934 Hom.: 10688 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.387

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.366 AC: 55592 AN: 152054 Hom.: 10695 Cov.: 32 AF XY: 0.363 AC XY: 26962 AN XY: 74318

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.393

Alfa AF: 0.402 Hom.: 12073

Bravo AF: 0.355

Asia WGS AF: 0.367 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.0
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs10917431; hg19: chr1-24174093; COSMIC: COSV65698845;