19-48704000-T-C

Variant names:

• chr19-48704000-T-C
• rs603985
• NM_000511.6:c.*12T>C

Variant summary

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

The NM_000511.6(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 NM_000511.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 29 publications found

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]

LOC105447645 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000511.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	NM_000511.6	MANE Select	c.*12T>C		3_prime_UTR	Exon 2 of 2	NP_000502.4
	FUT2	NM_001097638.3		c.*12T>C		3_prime_UTR	Exon 2 of 2	NP_001091107.1
	LOC105447645	NR_131188.1		n.-152A>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.*12T>C		3_prime_UTR	Exon 2 of 2	ENSP00000387498.2
	FUT2	ENST00000522966.2	TSL:2	c.*12T>C		3_prime_UTR	Exon 2 of 2	ENSP00000430227.2

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

GnomAD2 exomes AF: 0.403 AC: 100754 AN: 249804 AF XY: 0.407

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 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

African (AFR) AF: 0.511 AC: 17045 AN: 33380

American (AMR) AF: 0.292 AC: 13045 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 12327 AN: 26118

East Asian (EAS) AF: 0.00237 AC: 94 AN: 39660

South Asian (SAS) AF: 0.322 AC: 27540 AN: 85638

European-Finnish (FIN) AF: 0.421 AC: 22377 AN: 53092

Middle Eastern (MID) AF: 0.540 AC: 3105 AN: 5750

European-Non Finnish (NFE) AF: 0.526 AC: 582337 AN: 1107330

Other (OTH) AF: 0.486 AC: 29193 AN: 60114

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

African (AFR) AF: 0.508 AC: 20971 AN: 41320

American (AMR) AF: 0.386 AC: 5882 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1635 AN: 3468

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5162

South Asian (SAS) AF: 0.296 AC: 1403 AN: 4732

European-Finnish (FIN) AF: 0.408 AC: 4279 AN: 10480

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34269 AN: 67848

Other (OTH) AF: 0.474 AC: 1000 AN: 2108

Alfa AF: 0.483 Hom.: 15405

Bravo AF: 0.464

Asia WGS AF: 0.156 AC: 541 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.9
DANN	Benign	0.34
PhyloP100		0.027
Mutation Taster		=99/1	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: rs603985; hg19: chr19-49207257;