19-48703346-C-T

Variant names:

• chr19-48703346-C-T
• rs281377
• NM_000511.6:c.390C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000511.6(FUT2):​c.390C>T​(p.Asn130Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,612,590 control chromosomes in the GnomAD database, including 171,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14954 hom., cov: 32)
  • Exomes 𝑓: 0.45 (156612 hom.)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0310
• Publications: 83 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 19-48703346-C-T is Benign according to our data. Variant chr19-48703346-C-T is described in ClinVar as Benign. ClinVar VariationId is 1288280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.031 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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.390C>T	p.Asn130Asn	synonymous	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.390C>T	p.Asn130Asn	synonymous	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.503G>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.390C>T	p.Asn130Asn	synonymous	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.390C>T	p.Asn130Asn	synonymous	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.390C>T	p.Asn130Asn	synonymous	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64398 AN: 151762 Hom.: 14955 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.420

GnomAD2 exomes AF: 0.494 AC: 123629 AN: 250030 AF XY: 0.492

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.869

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.454 AC: 662748 AN: 1460712 Hom.: 156612 Cov.: 86 AF XY: 0.456 AC XY: 331037 AN XY: 726626

African (AFR) AF: 0.256 AC: 8586 AN: 33480

American (AMR) AF: 0.548 AC: 24503 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 12713 AN: 26132

East Asian (EAS) AF: 0.845 AC: 33520 AN: 39688

South Asian (SAS) AF: 0.467 AC: 40109 AN: 85882

European-Finnish (FIN) AF: 0.505 AC: 26647 AN: 52762

Middle Eastern (MID) AF: 0.411 AC: 2370 AN: 5766

European-Non Finnish (NFE) AF: 0.438 AC: 487538 AN: 1111948

Other (OTH) AF: 0.444 AC: 26762 AN: 60340

GnomAD4 genome AF: 0.424 AC: 64424 AN: 151878 Hom.: 14954 Cov.: 32 AF XY: 0.431 AC XY: 31961 AN XY: 74196

African (AFR) AF: 0.263 AC: 10920 AN: 41462

American (AMR) AF: 0.494 AC: 7542 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3468

East Asian (EAS) AF: 0.850 AC: 4383 AN: 5158

South Asian (SAS) AF: 0.465 AC: 2199 AN: 4724

European-Finnish (FIN) AF: 0.508 AC: 5364 AN: 10564

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30867 AN: 67928

Other (OTH) AF: 0.420 AC: 886 AN: 2110

Alfa AF: 0.444 Hom.: 18851

Bravo AF: 0.418

Asia WGS AF: 0.642 AC: 2188 AN: 3416

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FUT2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		-0.031
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: rs281377; hg19: chr19-49206603; COSMIC: COSV67179097;