14-65561787-T-C

Variant names:

• chr14-65561787-T-C
• rs3825639
• NM_001371533.1:c.203+21T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001371533.1(FUT8):​c.203+21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,579,590 control chromosomes in the GnomAD database, including 382,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37619 hom., cov: 32)
  • Exomes 𝑓: 0.69 (345008 hom.)
• Consequence: FUT8 NM_001371533.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0890
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-65561787-T-C is Benign according to our data. Variant chr14-65561787-T-C is described in ClinVar as [Benign]. Clinvar id is 1238047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT8	NM_001371533.1	c.203+21T>C		intron_variant	Intron 3 of 10	ENST00000673929.1	NP_001358462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT8	ENST00000673929.1	c.203+21T>C		intron_variant	Intron 3 of 10		NM_001371533.1	ENSP00000501213.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106416 AN: 151884 Hom.: 37575 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.671

GnomAD2 exomes AF: 0.705 AC: 174678 AN: 247886 AF XY: 0.704

Gnomad AFR exome AF: 0.734

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.690

Gnomad EAS exome AF: 0.902

Gnomad FIN exome AF: 0.618

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.693 AC: 989848 AN: 1427588 Hom.: 345008 Cov.: 24 AF XY: 0.695 AC XY: 494892 AN XY: 712242

African (AFR) AF: 0.726 AC: 23767 AN: 32734

American (AMR) AF: 0.706 AC: 31361 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17735 AN: 25816

East Asian (EAS) AF: 0.902 AC: 35559 AN: 39416

South Asian (SAS) AF: 0.771 AC: 65890 AN: 85418

European-Finnish (FIN) AF: 0.620 AC: 32987 AN: 53174

Middle Eastern (MID) AF: 0.633 AC: 3594 AN: 5682

European-Non Finnish (NFE) AF: 0.682 AC: 737242 AN: 1081692

Other (OTH) AF: 0.704 AC: 41713 AN: 59232

GnomAD4 genome AF: 0.701 AC: 106517 AN: 152002 Hom.: 37619 Cov.: 32 AF XY: 0.702 AC XY: 52166 AN XY: 74300

African (AFR) AF: 0.731 AC: 30314 AN: 41460

American (AMR) AF: 0.701 AC: 10689 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2400 AN: 3470

East Asian (EAS) AF: 0.900 AC: 4663 AN: 5182

South Asian (SAS) AF: 0.775 AC: 3729 AN: 4814

European-Finnish (FIN) AF: 0.609 AC: 6431 AN: 10562

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46027 AN: 67954

Other (OTH) AF: 0.675 AC: 1425 AN: 2112

Alfa AF: 0.687 Hom.: 12616

Bravo AF: 0.707

Asia WGS AF: 0.847 AC: 2944 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.62
PhyloP100		-0.089
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3825639; hg19: chr14-66028505;