19-5843598-T-C

Variant names:

• chr19-5843598-T-C
• rs874232
• ENST00000303225.12:c.*156A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000303225.12(FUT3):​c.*156A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,454,892 control chromosomes in the GnomAD database, including 150,382 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15127 hom., cov: 31)
  • Exomes 𝑓: 0.45 (135255 hom.)
• Consequence: FUT3 ENST00000303225.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 9 publications found

Genes affected

FUT3 (HGNC:4014): (fucosyltransferase 3 (Lewis blood group)) The Lewis histo-blood group system comprises a set of fucosylated glycosphingolipids that are synthesized by exocrine epithelial cells and circulate in body fluids. The glycosphingolipids function in embryogenesis, tissue differentiation, tumor metastasis, inflammation, and bacterial adhesion. They are secondarily absorbed to red blood cells giving rise to their Lewis phenotype. This gene is a member of the fucosyltransferase family, which catalyzes the addition of fucose to precursor polysaccharides in the last step of Lewis antigen biosynthesis. It encodes an enzyme with alpha(1,3)-fucosyltransferase and alpha(1,4)-fucosyltransferase activities. Mutations in this gene are responsible for the majority of Lewis antigen-negative phenotypes. Differences in the expression of this gene are associated with host susceptibility to viral infection. [provided by RefSeq, Aug 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT3	NM_000149.4	c.*156A>G		3_prime_UTR_variant	Exon 3 of 3		NP_000140.1
FUT3	NM_001097639.3	c.*156A>G		3_prime_UTR_variant	Exon 3 of 3		NP_001091108.3
FUT3	NM_001097640.3	c.*156A>G		3_prime_UTR_variant	Exon 3 of 3		NP_001091109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT3	ENST00000303225.12	c.*156A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.*156A>G		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.*156A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.*156A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66627 AN: 151652 Hom.: 15101 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.450 AC: 586887 AN: 1303122 Hom.: 135255 Cov.: 20 AF XY: 0.454 AC XY: 295647 AN XY: 651734

African (AFR) AF: 0.357 AC: 10895 AN: 30506

American (AMR) AF: 0.588 AC: 24582 AN: 41820

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 11167 AN: 23144

East Asian (EAS) AF: 0.687 AC: 26716 AN: 38888

South Asian (SAS) AF: 0.571 AC: 44290 AN: 77550

European-Finnish (FIN) AF: 0.455 AC: 18899 AN: 41540

Middle Eastern (MID) AF: 0.463 AC: 1750 AN: 3780

European-Non Finnish (NFE) AF: 0.427 AC: 422964 AN: 991006

Other (OTH) AF: 0.467 AC: 25624 AN: 54888

GnomAD4 genome AF: 0.439 AC: 66681 AN: 151770 Hom.: 15127 Cov.: 31 AF XY: 0.447 AC XY: 33129 AN XY: 74174

African (AFR) AF: 0.361 AC: 14939 AN: 41392

American (AMR) AF: 0.532 AC: 8111 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1657 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3591 AN: 5144

South Asian (SAS) AF: 0.585 AC: 2807 AN: 4802

European-Finnish (FIN) AF: 0.455 AC: 4795 AN: 10532

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29315 AN: 67882

Other (OTH) AF: 0.457 AC: 961 AN: 2104

Alfa AF: 0.438 Hom.: 43071

Bravo AF: 0.443

Asia WGS AF: 0.633 AC: 2200 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.057
DANN	Benign	0.43
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs874232; hg19: chr19-5843609;