rs632111

Positions:

• chr19-48705721-A-G
• chr19-48705721-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000511.6(FUT2):​c.*1733A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 166,880 control chromosomes in the GnomAD database, including 17,310 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 (15995 hom., cov: 31)
  • Exomes 𝑓: 0.42 (1315 hom.)
• Consequence: FUT2 NM_000511.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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]

MAMSTR (HGNC:26689): (MEF2 activating motif and SAP domain containing transcriptional regulator) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of myotube differentiation and positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT2	NM_000511.6	c.*1733A>G		3_prime_UTR_variant	2/2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.*1733A>G		3_prime_UTR_variant	2/2		NP_001091107.1
MAMSTR	XM_047438640.1	c.*1547T>C		3_prime_UTR_variant	7/7		XP_047294596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3	c.*1733A>G		3_prime_UTR_variant	2/2	1	NM_000511.6	ENSP00000387498.2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67568 AN: 151780 Hom.: 16002 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.416 AC: 6237 AN: 14984 Hom.: 1315 Cov.: 0 AF XY: 0.413 AC XY: 2942 AN XY: 7116

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.433

GnomAD4 genome AF: 0.445 AC: 67570 AN: 151896 Hom.: 15995 Cov.: 31 AF XY: 0.433 AC XY: 32140 AN XY: 74210

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.462

Alfa AF: 0.474 Hom.: 12835

Bravo AF: 0.445

Asia WGS AF: 0.137 AC: 474 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.80

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: rs632111; hg19: chr19-49208978; COSMIC: COSV67179234; COSMIC: COSV67179234;