chr14-65561347-G-A

Variant names:

• chr14-65561347-G-A
• rs45549535
• ENST00000342677.10:n.-217G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001371533.1(FUT8):​c.-217G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 538,170 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (54 hom., cov: 32)
  • Exomes 𝑓: 0.028 (320 hom.)
• Consequence: FUT8 NM_001371533.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.854
• Publications: 1 publications found

Genes affected

FUT8 (HGNC:4019): (fucosyltransferase 8) This gene encodes an enzyme belonging to the family of fucosyltransferases. The product of this gene catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides. This enzyme is distinct from other fucosyltransferases which catalyze alpha1-2, alpha1-3, and alpha1-4 fucose addition. The expression of this gene may contribute to the malignancy of cancer cells and to their invasive and metastatic capabilities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

FUT8 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation with defective fucosylation 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 14-65561347-G-A is Benign according to our data. Variant chr14-65561347-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1706869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT8	NM_001371533.1	c.-217G>A		5_prime_UTR_variant	Exon 3 of 11	ENST00000673929.1	NP_001358462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT8	ENST00000673929.1	c.-217G>A		5_prime_UTR_variant	Exon 3 of 11		NM_001371533.1	ENSP00000501213.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3145 AN: 152048 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0280 AC: 10800 AN: 386004 Hom.: 320 Cov.: 3 AF XY: 0.0268 AC XY: 5401 AN XY: 201484

African (AFR) AF: 0.0152 AC: 174 AN: 11478

American (AMR) AF: 0.0162 AC: 280 AN: 17232

Ashkenazi Jewish (ASJ) AF: 0.0724 AC: 880 AN: 12154

East Asian (EAS) AF: 0.114 AC: 3270 AN: 28642

South Asian (SAS) AF: 0.00856 AC: 274 AN: 31996

European-Finnish (FIN) AF: 0.0160 AC: 428 AN: 26668

Middle Eastern (MID) AF: 0.0133 AC: 23 AN: 1734

European-Non Finnish (NFE) AF: 0.0209 AC: 4863 AN: 233072

Other (OTH) AF: 0.0264 AC: 608 AN: 23028

GnomAD4 genome AF: 0.0207 AC: 3143 AN: 152166 Hom.: 54 Cov.: 32 AF XY: 0.0201 AC XY: 1499 AN XY: 74394

African (AFR) AF: 0.0130 AC: 541 AN: 41516

American (AMR) AF: 0.0166 AC: 253 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.0675 AC: 349 AN: 5172

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4818

European-Finnish (FIN) AF: 0.0166 AC: 176 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0214 AC: 1453 AN: 67998

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.0232 Hom.: 119

Bravo AF: 0.0209

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 06, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs45549535; hg19: chr14-66028065;