19-48703374-A-T

Variant names:

• chr19-48703374-A-T
• rs1047781
• NM_000511.6:c.418A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000511.6(FUT2):​c.418A>T​(p.Ile140Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,613,090 control chromosomes in the GnomAD database, including 4,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (535 hom., cov: 32)
  • Exomes 𝑓: 0.014 (4098 hom.)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:2 O:1
• Conservation: PhyloP100: 2.16
• Publications: 106 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004746765).
• BP6: Variant 19-48703374-A-T is Benign according to our data. Variant chr19-48703374-A-T is described in ClinVar as Benign. ClinVar VariationId is 12946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 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.418A>T	p.Ile140Phe	missense	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.418A>T	p.Ile140Phe	missense	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.475T>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.418A>T	p.Ile140Phe	missense	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.418A>T	p.Ile140Phe	missense	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.418A>T	p.Ile140Phe	missense	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2562 AN: 152064 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.0364 AC: 9127 AN: 250590 AF XY: 0.0338

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.472

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.0183

GnomAD4 exome AF: 0.0138 AC: 20210 AN: 1460908 Hom.: 4098 Cov.: 76 AF XY: 0.0135 AC XY: 9825 AN XY: 726718

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.000827 AC: 37 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 32 AN: 26128

East Asian (EAS) AF: 0.440 AC: 17485 AN: 39694

South Asian (SAS) AF: 0.0101 AC: 867 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.000196 AC: 218 AN: 1111960

Other (OTH) AF: 0.0254 AC: 1532 AN: 60338

GnomAD4 genome AF: 0.0168 AC: 2558 AN: 152182 Hom.: 535 Cov.: 32 AF XY: 0.0192 AC XY: 1432 AN XY: 74396

African (AFR) AF: 0.00108 AC: 45 AN: 41574

American (AMR) AF: 0.00366 AC: 56 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2302 AN: 5160

South Asian (SAS) AF: 0.0190 AC: 90 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68024

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0150 Hom.: 375

Bravo AF: 0.0198

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0349 AC: 4232

Asia WGS AF: 0.164 AC: 558 AN: 3412

EpiCase AF: 0.000600

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SECRETOR/NONSECRETOR POLYMORPHISM, JAPANESE TYPE (1)
-	-	-	Familial Otitis Media (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.6	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		2.2
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.25
MPC		0.89
ClinPred		0.043	T
GERP RS		3.8
Varity_R		0.44
gMVP		0.56
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: rs1047781; hg19: chr19-49206631; COSMIC: COSV67179407;