Genetic Variant FUT4:p.Arg34Trp (chr11-94544233-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002033.4(FUT4):c.100C>T(p.Arg34Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,323,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

FUT4
NM_002033.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.91

Publications

3 publications found

Variant links:

Genes affected

FUT4 (HGNC:4015): (fucosyltransferase 4) The product of this gene transfers fucose to N-acetyllactosamine polysaccharides to generate fucosylated carbohydrate structures. It catalyzes the synthesis of the non-sialylated antigen, Lewis x (CD15). [provided by RefSeq, Jan 2009]

FUT4 links:

PIWIL4 (HGNC:18444): (piwi like RNA-mediated gene silencing 4) PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

PIWIL4 links:

ENSG00000304830 (HGNC:):

ENSG00000304830 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05448219).

BP6

Variant 11-94544233-C-T is Benign according to our data. Variant chr11-94544233-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2570331.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT4	NM_002033.4	MANE Select	c.100C>T	p.Arg34Trp	missense	Exon 1 of 1	NP_002024.1	P22083-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT4	ENST00000358752.4	TSL:6 MANE Select	c.100C>T	p.Arg34Trp	missense	Exon 1 of 1	ENSP00000351602.2	P22083-1
PIWIL4	ENST00000543336.5	TSL:2	n.-121+244C>T		intron	N/A	ENSP00000444575.1	Q7Z3Z4-3
ENSG00000304830	ENST00000806516.1		n.-89G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000300

AC:

AN:

99870

AF XY:

0.0000529

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000669

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1323956

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

650726

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26296

American (AMR)

AF:

0.00

AC:

AN:

24682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19406

East Asian (EAS)

AF:

0.00

AC:

AN:

31090

South Asian (SAS)

AF:

0.00

AC:

AN:

67352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46204

Middle Eastern (MID)

AF:

0.000267

AC:

AN:

3752

European-Non Finnish (NFE)

AF:

0.0000219

AC:

AN:

1051236

Other (OTH)

AF:

0.00

AC:

AN:

53938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000893

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.092

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-1.9

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.68

REVEL

Benign

0.024

Sift

Benign

0.11

Sift4G

Uncertain

0.021

Polyphen

0.0

Vest4

0.075

MutPred

0.18

Loss of methylation at R34 (P = 0.0279)

MVP

0.20

MPC

0.82

ClinPred

0.10

GERP RS

-2.5

PromoterAI

0.0059

Neutral

(source)

Varity_R

0.057

gMVP

0.11

Mutation Taster

=92/8

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over