14-65677062-A-G

Variant names:

• chr14-65677062-A-G
• rs17102844
• NM_001371533.1:c.835+7582A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371533.1(FUT8):​c.835+7582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 151,516 control chromosomes in the GnomAD database, including 514 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 0.062 (514 hom., cov: 30)
• Consequence: FUT8 NM_001371533.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 3 publications found

Genes affected

FUT8 (HGNC:4019): (fucosyltransferase 8) This gene encodes an enzyme belonging to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

FUT8 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation with defective fucosylation 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT8	NM_001371533.1	c.835+7582A>G		intron_variant	Intron 7 of 10	ENST00000673929.1	NP_001358462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT8	ENST00000673929.1	c.835+7582A>G		intron_variant	Intron 7 of 10		NM_001371533.1	ENSP00000501213.1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9318 AN: 151398 Hom.: 514 Cov.: 30

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0436

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

GnomAD4 genome AF: 0.0616 AC: 9327 AN: 151516 Hom.: 514 Cov.: 30 AF XY: 0.0604 AC XY: 4472 AN XY: 74032

African (AFR) AF: 0.143 AC: 5902 AN: 41232

American (AMR) AF: 0.0289 AC: 440 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 292 AN: 3456

East Asian (EAS) AF: 0.137 AC: 702 AN: 5124

South Asian (SAS) AF: 0.0327 AC: 157 AN: 4796

European-Finnish (FIN) AF: 0.0189 AC: 198 AN: 10474

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0226 AC: 1532 AN: 67910

Other (OTH) AF: 0.0432 AC: 91 AN: 2108

Alfa AF: 0.0487 Hom.: 46

Bravo AF: 0.0665

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.66
PhyloP100		0.020
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: rs17102844; hg19: chr14-66143780;