chr19-48703364-A-G

Variant names:

• chr19-48703364-A-G
• rs1800026
• NM_000511.6:c.408A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000511.6(FUT2):​c.408A>G​(p.Glu136Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,611,408 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (10 hom.)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44
• Publications: 5 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-48703364-A-G is Benign according to our data. Variant chr19-48703364-A-G is described in ClinVar as [Benign]. Clinvar id is 714890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00602 (916/152146) while in subpopulation AFR AF = 0.0194 (806/41560). AF 95% confidence interval is 0.0183. There are 19 homozygotes in GnomAd4. There are 452 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6	c.408A>G	p.Glu136Glu	synonymous_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.408A>G	p.Glu136Glu	synonymous_variant	Exon 2 of 2		NP_001091107.1
LOC105447645	NR_131188.1	n.485T>C		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3	c.408A>G	p.Glu136Glu	synonymous_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2
FUT2	ENST00000522966.2	c.408A>G	p.Glu136Glu	synonymous_variant	Exon 2 of 2	2		ENSP00000430227.2

Frequencies

GnomAD3 genomes AF: 0.00597 AC: 907 AN: 152030 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00185 AC: 462 AN: 250230 AF XY: 0.00159

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000753

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.00124 AC: 1807 AN: 1459262 Hom.: 10 Cov.: 77 AF XY: 0.00119 AC XY: 861 AN XY: 725960

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0200 AC: 668 AN: 33476

American (AMR) AF: 0.000962 AC: 43 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26130

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39688

South Asian (SAS) AF: 0.000349 AC: 30 AN: 85888

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52744

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.000773 AC: 858 AN: 1110578

Other (OTH) AF: 0.00212 AC: 128 AN: 60280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00602 AC: 916 AN: 152146 Hom.: 19 Cov.: 32 AF XY: 0.00608 AC XY: 452 AN XY: 74402

African (AFR) AF: 0.0194 AC: 806 AN: 41560

American (AMR) AF: 0.00177 AC: 27 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67974

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00404 Hom.: 1

Bravo AF: 0.00705

Asia WGS AF: 0.0160 AC: 55 AN: 3416

EpiCase AF: 0.000765

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.46
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs1800026; hg19: chr19-49206621;