19-48750460-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001384359.1(FUT1):c.822C>A(p.Thr274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,614,156 control chromosomes in the GnomAD database, including 1,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (521 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (501 hom.)
• Consequence: FUT1 NM_001384359.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0970

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-48750460-G-T is Benign according to our data. Variant chr19-48750460-G-T is described in ClinVar as [Benign]. Clinvar id is 3055812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.097 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT1	NM_001384359.1	c.822C>A	p.Thr274=	synonymous_variant	2/2	ENST00000645652.2
FUT1	NM_000148.4	c.822C>A	p.Thr274=	synonymous_variant	4/4
FUT1	NM_001329877.1	c.822C>A	p.Thr274=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT1	ENST00000645652.2	c.822C>A	p.Thr274=	synonymous_variant	2/2		NM_001384359.1	P1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6948 AN: 152166 Hom.: 519 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0315

GnomAD3 exomes AF: 0.0121 AC: 3044 AN: 251456 Hom.: 232 AF XY: 0.00898 AC XY: 1220 AN XY: 135910

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.00818

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00470 AC: 6875 AN: 1461872 Hom.: 501 Cov.: 33 AF XY: 0.00402 AC XY: 2925 AN XY: 727232

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00930

Gnomad4 ASJ exome AF: 0.000612

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000190

Gnomad4 OTH exome AF: 0.00960

GnomAD4 genome AF: 0.0458 AC: 6971 AN: 152284 Hom.: 521 Cov.: 33 AF XY: 0.0446 AC XY: 3322 AN XY: 74454

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0271 Hom.: 143

Bravo AF: 0.0534

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FUT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.72
Dann	Benign	0.72

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: rs838138; hg19: chr19-49253717;