19-48703346-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000511.6(FUT2):c.390C>T(p.Asn130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,612,590 control chromosomes in the GnomAD database, including 171,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14954 hom., cov: 32)
  • Exomes 𝑓: 0.45 (156612 hom.)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0310

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]

LOC105447645 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 19-48703346-C-T is Benign according to our data. Variant chr19-48703346-C-T is described in ClinVar as [Benign]. Clinvar id is 1288280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.031 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT2	NM_000511.6	c.390C>T	p.Asn130=	synonymous_variant	2/2	ENST00000425340.3
LOC105447645	NR_131188.1	n.503G>A		non_coding_transcript_exon_variant	1/1
FUT2	NM_001097638.3	c.390C>T	p.Asn130=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT2	ENST00000425340.3	c.390C>T	p.Asn130=	synonymous_variant	2/2	1	NM_000511.6	P1
FUT2	ENST00000522966.2	c.390C>T	p.Asn130=	synonymous_variant	2/2	2		P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64398 AN: 151762 Hom.: 14955 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.420

GnomAD3 exomes AF: 0.494 AC: 123629 AN: 250030 Hom.: 33028 AF XY: 0.492 AC XY: 66679 AN XY: 135472

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.869

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.454 AC: 662748 AN: 1460712 Hom.: 156612 Cov.: 86 AF XY: 0.456 AC XY: 331037 AN XY: 726626

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.486

Gnomad4 EAS exome AF: 0.845

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.505

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.424 AC: 64424 AN: 151878 Hom.: 14954 Cov.: 32 AF XY: 0.431 AC XY: 31961 AN XY: 74196

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.420

Alfa AF: 0.441 Hom.: 14467

Bravo AF: 0.418

Asia WGS AF: 0.642 AC: 2188 AN: 3416

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

FUT2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 22001757, 23002346) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	6.5
Dann	Benign	0.77

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: rs281377; hg19: chr19-49206603; COSMIC: COSV67179097;