19-48703998-A-G

Position:

• chr19-48703998-A-G

Variant summary

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

The NM_000511.6(FUT2):​c.*10A>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 0.484 in 1,607,944 control chromosomes in the GnomAD database, including 200,299 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 0.47 (17456 hom., cov: 32)
  • Exomes 𝑓: 0.49 (182843 hom.)
• Consequence: FUT2 NM_000511.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT2	NM_000511.6	c.*10A>G		3_prime_UTR_variant	2/2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.*10A>G		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.*10A>G		3_prime_UTR_variant	2/2	1	NM_000511.6	ENSP00000387498	P1
FUT2	ENST00000522966.2	c.*10A>G		3_prime_UTR_variant	2/2	2		ENSP00000430227	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70521 AN: 151492 Hom.: 17460 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.479

GnomAD3 exomes AF: 0.404 AC: 101026 AN: 249890 Hom.: 23606 AF XY: 0.407 AC XY: 55107 AN XY: 135242

Gnomad AFR exome AF: 0.520

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.00431

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: 707951 AN: 1456336 Hom.: 182843 Cov.: 36 AF XY: 0.481 AC XY: 348260 AN XY: 724614

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.00242

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.465 AC: 70533 AN: 151608 Hom.: 17456 Cov.: 32 AF XY: 0.453 AC XY: 33545 AN XY: 74050

Gnomad4 AFR AF: 0.521

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: 0.475

Alfa AF: 0.501 Hom.: 9878

Bravo AF: 0.468

Asia WGS AF: 0.157 AC: 543 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.62
DANN	Benign	0.28

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: rs485073; hg19: chr19-49207255;