rs2071699

Positions:

• chr19-48751247-G-A
• chr19-48751247-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.032 (311 hom., cov: 33)
  • Exomes 𝑓: 0.035 (3493 hom.)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 3056653.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
FUT1	NM_001384359.1	c.35C>T	p.Ala12Val	missense_variant	2/2	ENST00000645652.2
FUT1	NM_000148.4	c.35C>T	p.Ala12Val	missense_variant	4/4
FUT1	NM_001329877.1	c.35C>T	p.Ala12Val	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT1	ENST00000645652.2	c.35C>T	p.Ala12Val	missense_variant	2/2		NM_001384359.1	P1

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4829 AN: 152170 Hom.: 313 Cov.: 33

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

GnomAD3 exomes AF: 0.0590 AC: 14801 AN: 250760 Hom.: 1119 AF XY: 0.0587 AC XY: 7968 AN XY: 135658

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 SAS exome AF: 0.101

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.: 33 AF XY: 0.0363 AC XY: 26409 AN XY: 727170

Gnomad4 AFR exome AF: 0.00335

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.0996

Gnomad4 FIN exome AF: 0.0434

Gnomad4 NFE exome AF: 0.0173

Gnomad4 OTH exome AF: 0.0398

GnomAD4 genome AF: 0.0317 AC: 4821 AN: 152288 Hom.: 311 Cov.: 33 AF XY: 0.0358 AC XY: 2669 AN XY: 74464

Gnomad4 AFR AF: 0.00411

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0225 Hom.: 117

Bravo AF: 0.0302

TwinsUK AF: 0.0154 AC: 57

ALSPAC AF: 0.0187 AC: 72

ESP6500AA AF: 0.00363 AC: 16

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: criteria provided, single submitter

Submissions by phenotype

FUT1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2020

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	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.54	D
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.94	P
PrimateAI	Benign	0.27	T
Polyphen		0.10	B;B
Vest4		0.023
MPC		0.43
ClinPred		0.0051	T
GERP RS		-1.3
Varity_R		0.045
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs2071699; hg19: chr19-49254504; COSMIC: COSV55810009; COSMIC: COSV55810009;