19-48705608-G-A

Variant names:

• chr19-48705608-G-A
• rs504963
• NM_000511.6:c.*1620G>A

Variant summary

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

The NM_000511.6(FUT2):​c.*1620G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 166,932 control chromosomes in the GnomAD database, including 19,219 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 0.47 (17914 hom., cov: 32)
  • Exomes 𝑓: 0.41 (1305 hom.)
• Consequence: FUT2 NM_000511.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 69 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]

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 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.*1620G>A		3_prime_UTR	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.*1620G>A		3_prime_UTR	Exon 2 of 2	NP_001091107.1	Q10981

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.*1620G>A		3_prime_UTR	Exon 2 of 2	ENSP00000387498.2	Q10981

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71392 AN: 151806 Hom.: 17901 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.414 AC: 6214 AN: 15010 Hom.: 1305 Cov.: 0 AF XY: 0.411 AC XY: 2934 AN XY: 7132

African (AFR) AF: 0.333 AC: 2 AN: 6

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.421 AC: 59 AN: 140

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.413 AC: 6059 AN: 14670

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.521 AC: 49 AN: 94

Other (OTH) AF: 0.436 AC: 41 AN: 94

GnomAD4 genome AF: 0.470 AC: 71440 AN: 151922 Hom.: 17914 Cov.: 32 AF XY: 0.457 AC XY: 33961 AN XY: 74244

African (AFR) AF: 0.544 AC: 22529 AN: 41438

American (AMR) AF: 0.390 AC: 5946 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3470

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1413 AN: 4754

European-Finnish (FIN) AF: 0.404 AC: 4271 AN: 10574

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34115 AN: 67948

Other (OTH) AF: 0.483 AC: 1017 AN: 2104

Alfa AF: 0.484 Hom.: 86227

Bravo AF: 0.474

Asia WGS AF: 0.161 AC: 556 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.61
DANN	Benign	0.73
PhyloP100		-0.49
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: rs504963; hg19: chr19-49208865; COSMIC: COSV67179263; COSMIC: COSV67179263;