dbSNP rs35137471: FUT8:p.Leu190Leu (chr14-65629579-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001371533.1(FUT8):c.570G>A(p.Leu190Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,110 control chromosomes in the GnomAD database, including 909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 69 hom., cov: 32)

Exomes 𝑓: 0.024 ( 840 hom. )

Consequence

FUT8
NM_001371533.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.30

Publications

4 publications found

Variant links:

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)

FUT8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 14-65629579-G-A is Benign according to our data. Variant chr14-65629579-G-A is described in ClinVar as Benign. ClinVar VariationId is 402888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371533.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FUT8	NM_001371533.1	MANE Select	c.570G>A	p.Leu190Leu	synonymous	Exon 6 of 11	NP_001358462.1
FUT8	NM_001371536.1		c.672G>A	p.Leu224Leu	synonymous	Exon 7 of 12	NP_001358465.1
FUT8	NM_001371534.1		c.570G>A	p.Leu190Leu	synonymous	Exon 7 of 12	NP_001358463.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FUT8	ENST00000673929.1	MANE Select	c.570G>A	p.Leu190Leu	synonymous	Exon 6 of 11	ENSP00000501213.1
FUT8	ENST00000360689.9	TSL:1	c.570G>A	p.Leu190Leu	synonymous	Exon 6 of 11	ENSP00000353910.5
FUT8	ENST00000394586.6	TSL:1	c.570G>A	p.Leu190Leu	synonymous	Exon 5 of 10	ENSP00000378087.2

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3174

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00551

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0746

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0360

AC:

9061

AN:

251380

AF XY:

0.0319

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0240

AC:

35028

AN:

1460888

Hom.:

840

Cov.:

AF XY:

0.0232

AC XY:

16892

AN XY:

726818

show subpopulations

African (AFR)

AF:

0.00323

AC:

108

AN:

33468

American (AMR)

AF:

0.138

AC:

6190

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0214

AC:

560

AN:

26120

East Asian (EAS)

AF:

0.000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.0236

AC:

2034

AN:

86232

European-Finnish (FIN)

AF:

0.0188

AC:

1002

AN:

53406

Middle Eastern (MID)

AF:

0.0187

AC:

108

AN:

5768

European-Non Finnish (NFE)

AF:

0.0213

AC:

23668

AN:

1111134

Other (OTH)

AF:

0.0222

AC:

1338

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

1507

3013

4520

6026

7533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

956

1912

2868

3824

4780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0209

AC:

3180

AN:

152222

Hom.:

Cov.:

AF XY:

0.0219

AC XY:

1627

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00549

AC:

228

AN:

41532

American (AMR)

AF:

0.0748

AC:

1143

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3470

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0232

AC:

112

AN:

4830

European-Finnish (FIN)

AF:

0.0176

AC:

186

AN:

10598

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0202

AC:

1376

AN:

68012

Other (OTH)

AF:

0.0209

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

151

301

452

602

753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0217

Hom.:

144

Bravo

AF:

0.0263

EpiCase

AF:

0.0204

EpiControl

AF:

0.0187

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

FUT8-related disorder

Benign:1

Jun 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.8

(source)

DANN

Benign

0.67

PhyloP100

2.3

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over