chr14-65615855-A-G

Variant names:

• chr14-65615855-A-G
• rs8012278
• NM_001371533.1:c.204-123A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001371533.1(FUT8):​c.204-123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 638,516 control chromosomes in the GnomAD database, including 62,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (11922 hom., cov: 33)
  • Exomes 𝑓: 0.44 (50249 hom.)
• Consequence: FUT8 NM_001371533.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.848
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-65615855-A-G is Benign according to our data. Variant chr14-65615855-A-G is described in ClinVar as [Benign]. Clinvar id is 1236941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT8	NM_001371533.1	c.204-123A>G		intron_variant	Intron 3 of 10	ENST00000673929.1	NP_001358462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT8	ENST00000673929.1	c.204-123A>G		intron_variant	Intron 3 of 10		NM_001371533.1	ENSP00000501213.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53914 AN: 152042 Hom.: 11913 Cov.: 33

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.439 AC: 213416 AN: 486354 Hom.: 50249 AF XY: 0.436 AC XY: 111075 AN XY: 254858

African (AFR) AF: 0.0951 AC: 1236 AN: 12994

American (AMR) AF: 0.384 AC: 6397 AN: 16638

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 6125 AN: 13820

East Asian (EAS) AF: 0.154 AC: 4783 AN: 31104

South Asian (SAS) AF: 0.335 AC: 13832 AN: 41342

European-Finnish (FIN) AF: 0.463 AC: 18085 AN: 39080

Middle Eastern (MID) AF: 0.339 AC: 1232 AN: 3638

European-Non Finnish (NFE) AF: 0.499 AC: 150160 AN: 300792

Other (OTH) AF: 0.429 AC: 11566 AN: 26946

GnomAD4 genome AF: 0.354 AC: 53920 AN: 152162 Hom.: 11922 Cov.: 33 AF XY: 0.353 AC XY: 26234 AN XY: 74380

African (AFR) AF: 0.0969 AC: 4026 AN: 41538

American (AMR) AF: 0.373 AC: 5701 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1518 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1182 AN: 5172

South Asian (SAS) AF: 0.305 AC: 1469 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4786 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33858 AN: 67988

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.417 Hom.: 2472

Bravo AF: 0.339

Asia WGS AF: 0.247 AC: 856 AN: 3474

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

- -

Jul 27, 2018

GeneDx

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	-0.82
CADD	Benign	7.0
DANN	Benign	0.74
PhyloP100		0.85
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: rs8012278; hg19: chr14-66082573; COSMIC: COSV61281754;