19-5851325-A-G

Position:

• chr19-5851325-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382749.2(FUT3):​c.-140-4772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,772 control chromosomes in the GnomAD database, including 8,546 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 0.30 (8527 hom., cov: 29)
  • Exomes 𝑓: 0.35 (19 hom.)
• Consequence: FUT3 NM_001382749.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT3	NM_001097639.3	c.-206+65T>C		intron_variant		ENST00000709635.1
FUT3	NM_001382749.2	c.-140-4772T>C		intron_variant
LOC101928844	NR_110740.1	n.303-1179A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT3	ENST00000303225.12	c.-554+65T>C		intron_variant		1		P1
	ENST00000589276.1	n.303-1179A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45921 AN: 151402 Hom.: 8524 Cov.: 29

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.353 AC: 89 AN: 252 Hom.: 19 AF XY: 0.361 AC XY: 52 AN XY: 144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.303 AC: 45923 AN: 151520 Hom.: 8527 Cov.: 29 AF XY: 0.299 AC XY: 22086 AN XY: 73954

Gnomad4 AFR AF: 0.0891

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.279

Alfa AF: 0.381 Hom.: 4204

Bravo AF: 0.289

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.23

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: rs11673407; hg19: chr19-5851336;