dbSNP rs2071699: FUT1:p.Ala12Val (chr19-48751247-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001384359.1(FUT1):c.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,614,056 control chromosomes in the GnomAD database, including 3,804 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.032 ( 311 hom., cov: 33)

Exomes 𝑓: 0.035 ( 3493 hom. )

Consequence

FUT1
NM_001384359.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0240

Publications

49 publications found

Variant links:

Genes affected

FUT1 (HGNC:4012): (fucosyltransferase 1 (H blood group)) This gene encodes a Golgi stack membrane protein that is involved in the creation of a precursor of the H antigen, which is required for the final step in the synthesis of soluble A and B antigens. This is one of two genes encoding the galactoside 2-L-fucosyltransferase enzyme. Mutations in this gene are a cause of the H-Bombay blood group. [provided by RefSeq, Aug 2016]

FUT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031044483).

BP6

Variant 19-48751247-G-A is Benign according to our data. Variant chr19-48751247-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3056653.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT1	NM_001384359.1 link	c.35C>T	p.Ala12Val	missense_variant	Exon 2 of 2	ENST00000645652.2	NP_001371288.1
FUT1	NM_000148.4 link	c.35C>T	p.Ala12Val	missense_variant	Exon 4 of 4		NP_000139.1	P19526Q6IZA2
FUT1	NM_001329877.1 link	c.35C>T	p.Ala12Val	missense_variant	Exon 5 of 5		NP_001316806.1	P19526Q6IZA2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT1	ENST00000645652.2 link	c.35C>T	p.Ala12Val	missense_variant	Exon 2 of 2		NM_001384359.1	ENSP00000494643.1		P19526

Frequencies

GnomAD3 genomes

AF:

0.0317

AC:

4829

AN:

152170

Hom.:

313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.0590

AC:

14801

AN:

250760

AF XY:

0.0587

show subpopulations

Gnomad AFR exome

AF:

0.00315

Gnomad AMR exome

AF:

0.0805

Gnomad ASJ exome

AF:

0.0279

Gnomad EAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0486

GnomAD4 exome

AF:

0.0346

AC:

50600

AN:

1461768

Hom.:

3493

Cov.:

AF XY:

0.0363

AC XY:

26409

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.00335

AC:

112

AN:

33480

American (AMR)

AF:

0.0739

AC:

3302

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

739

AN:

26136

East Asian (EAS)

AF:

0.344

AC:

13638

AN:

39694

South Asian (SAS)

AF:

0.0996

AC:

8594

AN:

86254

European-Finnish (FIN)

AF:

0.0434

AC:

2315

AN:

53364

Middle Eastern (MID)

AF:

0.0411

AC:

237

AN:

5766

European-Non Finnish (NFE)

AF:

0.0173

AC:

19261

AN:

1111968

Other (OTH)

AF:

0.0398

AC:

2402

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2906

5811

8717

11622

14528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

960

1920

2880

3840

4800

<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:

0.0317

AC:

4821

AN:

152288

Hom.:

311

Cov.:

AF XY:

0.0358

AC XY:

2669

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00411

AC:

171

AN:

41566

American (AMR)

AF:

0.0360

AC:

551

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3472

East Asian (EAS)

AF:

0.291

AC:

1502

AN:

5168

South Asian (SAS)

AF:

0.113

AC:

542

AN:

4814

European-Finnish (FIN)

AF:

0.0447

AC:

475

AN:

10618

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0205

AC:

1398

AN:

68034

Other (OTH)

AF:

0.0284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

227

454

681

908

1135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0246

Hom.:

252

Bravo

AF:

0.0302

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0207

AC:

178

ExAC

AF:

0.0572

AC:

6946

Asia WGS

AF:

0.182

AC:

630

AN:

3478

EpiCase

AF:

0.0192

EpiControl

AF:

0.0208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FUT1-related disorder

Benign:1

Feb 25, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.61

.;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;L

PhyloP100

0.024

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.14

.;N

REVEL

Benign

0.029

Sift

Benign

0.064

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.10

B;B

Vest4

0.023

MPC

0.43

ClinPred

0.0051

GERP RS

-1.3

Varity_R

0.045

gMVP

0.44

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over