rs34304528

Variant names:

• chr19-5843565-C-T
• rs34304528
• ENST00000303225.12:c.*189G>A

Variant summary

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

The ENST00000303225.12(FUT3):​c.*189G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,109,484 control chromosomes in the GnomAD database, including 6,966 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 0.080 (652 hom., cov: 31)
  • Exomes 𝑓: 0.10 (6314 hom.)
• Consequence: FUT3 ENST00000303225.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT3	NM_000149.4	c.*189G>A		3_prime_UTR_variant	Exon 3 of 3		NP_000140.1
FUT3	NM_001097639.3	c.*189G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001091108.3
FUT3	NM_001097640.3	c.*189G>A		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.*189G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.*189G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.*189G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.*189G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12111 AN: 151956 Hom.: 652 Cov.: 31

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0818

GnomAD4 exome AF: 0.104 AC: 99958 AN: 957410 Hom.: 6314 Cov.: 13 AF XY: 0.102 AC XY: 49524 AN XY: 487498

African (AFR) AF: 0.0187 AC: 440 AN: 23522

American (AMR) AF: 0.0509 AC: 1655 AN: 32520

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 1160 AN: 18992

East Asian (EAS) AF: 0.000310 AC: 11 AN: 35514

South Asian (SAS) AF: 0.0236 AC: 1516 AN: 64238

European-Finnish (FIN) AF: 0.117 AC: 4061 AN: 34858

Middle Eastern (MID) AF: 0.101 AC: 311 AN: 3076

European-Non Finnish (NFE) AF: 0.124 AC: 86581 AN: 701022

Other (OTH) AF: 0.0967 AC: 4223 AN: 43668

GnomAD4 genome AF: 0.0796 AC: 12107 AN: 152074 Hom.: 652 Cov.: 31 AF XY: 0.0769 AC XY: 5716 AN XY: 74328

African (AFR) AF: 0.0219 AC: 910 AN: 41506

American (AMR) AF: 0.0676 AC: 1032 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 189 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4806

European-Finnish (FIN) AF: 0.105 AC: 1109 AN: 10590

Middle Eastern (MID) AF: 0.0828 AC: 24 AN: 290

European-Non Finnish (NFE) AF: 0.124 AC: 8427 AN: 67958

Other (OTH) AF: 0.0810 AC: 171 AN: 2112

Alfa AF: 0.0863 Hom.: 82

Bravo AF: 0.0774

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.92
DANN	Benign	0.81
PhyloP100		-0.29
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: rs34304528; hg19: chr19-5843576; COSMIC: COSV54605442; COSMIC: COSV54605442;