19-48702915-C-T

Variant names:

• chr19-48702915-C-T
• rs516246
• NM_000511.6:c.-2-40C>T

Variant summary

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

The NM_000511.6(FUT2):​c.-2-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,604,928 control chromosomes in the GnomAD database, including 179,278 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 0.44 (15725 hom., cov: 32)
  • Exomes 𝑓: 0.46 (163553 hom.)
• Consequence: FUT2 NM_000511.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 130 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	NM_000511.6	MANE Select	c.-2-40C>T		intron	N/A	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.-2-40C>T		intron	N/A	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.934G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.-2-40C>T		intron	N/A	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.-2-40C>T		intron	N/A	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.-2-40C>T		intron	N/A	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66959 AN: 151830 Hom.: 15732 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.00369

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.457

GnomAD2 exomes AF: 0.383 AC: 95557 AN: 249716 AF XY: 0.387

Gnomad AFR exome AF: 0.497

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.00295

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.460 AC: 668503 AN: 1452982 Hom.: 163553 Cov.: 30 AF XY: 0.455 AC XY: 329249 AN XY: 723334

African (AFR) AF: 0.499 AC: 16650 AN: 33340

American (AMR) AF: 0.277 AC: 12375 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 11646 AN: 26096

East Asian (EAS) AF: 0.00185 AC: 73 AN: 39462

South Asian (SAS) AF: 0.320 AC: 27261 AN: 85184

European-Finnish (FIN) AF: 0.375 AC: 19486 AN: 51922

Middle Eastern (MID) AF: 0.514 AC: 2958 AN: 5750

European-Non Finnish (NFE) AF: 0.497 AC: 550290 AN: 1106520

Other (OTH) AF: 0.463 AC: 27764 AN: 59990

GnomAD4 genome AF: 0.441 AC: 66963 AN: 151946 Hom.: 15725 Cov.: 32 AF XY: 0.429 AC XY: 31811 AN XY: 74226

African (AFR) AF: 0.497 AC: 20624 AN: 41480

American (AMR) AF: 0.368 AC: 5615 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3472

East Asian (EAS) AF: 0.00370 AC: 19 AN: 5140

South Asian (SAS) AF: 0.295 AC: 1404 AN: 4758

European-Finnish (FIN) AF: 0.367 AC: 3881 AN: 10564

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32445 AN: 67956

Other (OTH) AF: 0.451 AC: 951 AN: 2108

Alfa AF: 0.457 Hom.: 56491

Bravo AF: 0.444

Asia WGS AF: 0.141 AC: 489 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		0.24
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: rs516246; hg19: chr19-49206172;