rs1047781

Positions:

• chr19-48703374-A-C
• chr19-48703374-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000511.6(FUT2):​c.418A>C​(p.Ile140Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I140F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34353977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT2	NM_000511.6	c.418A>C	p.Ile140Leu	missense_variant	2/2	ENST00000425340.3	NP_000502.4
LOC105447645	NR_131188.1	n.475T>G		non_coding_transcript_exon_variant	1/1
FUT2	NM_001097638.3	c.418A>C	p.Ile140Leu	missense_variant	2/2		NP_001091107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3	c.418A>C	p.Ile140Leu	missense_variant	2/2	1	NM_000511.6	ENSP00000387498	P1
FUT2	ENST00000522966.2	c.418A>C	p.Ile140Leu	missense_variant	2/2	2		ENSP00000430227	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.037	.;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.72	.;.;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.9	.;L;L
MutationTaster	Benign	0.59	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.77	N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.017	.;B;B
Vest4		0.24, 0.27
MutPred		0.51		Gain of disorder (P = 0.1129);Gain of disorder (P = 0.1129);Gain of disorder (P = 0.1129);
MVP		0.93
MPC		0.23
ClinPred		0.15	T
GERP RS		3.8
Varity_R		0.23
gMVP		0.40

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: rs1047781; hg19: chr19-49206631;