Variant 19-48703267-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_000511.6(FUT2):c.311C>T(p.Ala104Val) variant causes a missense change. The variant allele was found at a frequency of 0.00187 in 1,613,000 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 112 hom. )

Consequence

FUT2
NM_000511.6 missense

Scores

Clinical Significance

confers sensitivity no assertion criteria provided O:1

Conservation

PhyloP100: 4.73

Variant links:

Genes affected

FUT2 (HGNC:4013): (fucosyltransferase 2 (H blood group)) This gene is one of two encoding the galactoside 2-L-fucosyltransferase enzyme. The encoded protein is important for the final step in the soluble ABO blood group antigen synthesis pathway. It is also involved in cell-cell interaction, cell surface expression, and cell proliferation. Mutations in this gene are a cause of the H-Bombay blood group where red blood cells lack the H antigen. [provided by RefSeq, May 2022]

FUT2 links:

LOC105447645 (HGNC:):

LOC105447645 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01712045).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0013 (198/152208) while in subpopulation SAS AF= 0.0194 (92/4738). AF 95% confidence interval is 0.0162. There are 3 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FUT2	NM_000511.6 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	2/2	ENST00000425340.3
LOC105447645	NR_131188.1 linkuse as main transcript	n.582G>A		non_coding_transcript_exon_variant	1/1
FUT2	NM_001097638.3 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT2	ENST00000425340.3 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	2/2	1	NM_000511.6	P1
FUT2	ENST00000522966.2 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0194

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00352

AC:

872

AN:

247802

Hom.:

AF XY:

0.00444

AC XY:

598

AN XY:

134642

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00300

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0208

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

AF:

0.00193

AC:

2820

AN:

1460792

Hom.:

112

Cov.:

AF XY:

0.00254

AC XY:

1845

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0206

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000634

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152208

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0194

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00150

Hom.:

Bravo

AF:

0.000812

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000933

AC:

ExAC

AF:

0.00386

AC:

468

EpiCase

AF:

0.00256

EpiControl

AF:

0.00308

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Familial Otitis Media

Other:1

confers sensitivity, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

.;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

.;.;D

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

.;M;M

MutationTaster

Benign

0.94

D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Pathogenic

0.78

Sift

Benign

0.039

D;T;T

Sift4G

Uncertain

0.019

D;T;T

Polyphen

1.0

.;D;D

Vest4

0.56, 0.82

MVP

0.98

MPC

0.73

ClinPred

0.051

GERP RS

4.2

Varity_R

0.29

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over