rs603985

Positions:

• chr19-48704000-T-C

Variant summary

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

The ENST00000425340.3(FUT2):​c.*12T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,607,326 control chromosomes in the GnomAD database, including 199,649 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 0.46 (17136 hom., cov: 32)
  • Exomes 𝑓: 0.49 (182513 hom.)
• Consequence: FUT2 ENST00000425340.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT2	NM_000511.6	c.*12T>C		3_prime_UTR_variant	2/2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.*12T>C		3_prime_UTR_variant	2/2		NP_001091107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3	c.*12T>C		3_prime_UTR_variant	2/2	1	NM_000511.6	ENSP00000387498	P1
FUT2	ENST00000522966.2	c.*12T>C		3_prime_UTR_variant	2/2	2		ENSP00000430227	P1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 69941 AN: 151458 Hom.: 17141 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00387

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.478

GnomAD3 exomes AF: 0.403 AC: 100754 AN: 249804 Hom.: 23466 AF XY: 0.407 AC XY: 55016 AN XY: 135236

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.00425

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.503

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.486 AC: 707063 AN: 1455752 Hom.: 182513 Cov.: 36 AF XY: 0.480 AC XY: 347879 AN XY: 724370

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.00237

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.462 AC: 69952 AN: 151574 Hom.: 17136 Cov.: 32 AF XY: 0.449 AC XY: 33265 AN XY: 74032

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.474

Alfa AF: 0.487 Hom.: 9678

Bravo AF: 0.464

Asia WGS AF: 0.156 AC: 541 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.9
DANN	Benign	0.34

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: rs603985; hg19: chr19-49207257;