rs35137471

Variant names:

• chr14-65629579-G-A
• rs35137471
• NM_001371533.1:c.570G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-65629579-G-A
• chr14-65629579-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001371533.1(FUT8):​c.570G>A​(p.Leu190Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,110 control chromosomes in the GnomAD database, including 909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (69 hom., cov: 32)
  • Exomes 𝑓: 0.024 (840 hom.)
• Consequence: FUT8 NM_001371533.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.30
• Publications: 4 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: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 14-65629579-G-A is Benign according to our data. Variant chr14-65629579-G-A is described in ClinVar as Benign. ClinVar VariationId is 402888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371533.1. 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
	FUT8	NM_001371533.1	MANE Select	c.570G>A	p.Leu190Leu	synonymous	Exon 6 of 11	NP_001358462.1	Q546E0
	FUT8	NM_001371536.1		c.672G>A	p.Leu224Leu	synonymous	Exon 7 of 12	NP_001358465.1
	FUT8	NM_001371534.1		c.570G>A	p.Leu190Leu	synonymous	Exon 7 of 12	NP_001358463.1	Q546E0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT8	ENST00000673929.1	MANE Select	c.570G>A	p.Leu190Leu	synonymous	Exon 6 of 11	ENSP00000501213.1	Q9BYC5-1
	FUT8	ENST00000360689.9	TSL:1	c.570G>A	p.Leu190Leu	synonymous	Exon 6 of 11	ENSP00000353910.5	Q9BYC5-1
	FUT8	ENST00000394586.6	TSL:1	c.570G>A	p.Leu190Leu	synonymous	Exon 5 of 10	ENSP00000378087.2	Q9BYC5-1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3174 AN: 152104 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.00551

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.0360 AC: 9061 AN: 251380 AF XY: 0.0319

Gnomad AFR exome AF: 0.00431

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0206

Gnomad OTH exome AF: 0.0261

GnomAD4 exome AF: 0.0240 AC: 35028 AN: 1460888 Hom.: 840 Cov.: 29 AF XY: 0.0232 AC XY: 16892 AN XY: 726818

African (AFR) AF: 0.00323 AC: 108 AN: 33468

American (AMR) AF: 0.138 AC: 6190 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 560 AN: 26120

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39686

South Asian (SAS) AF: 0.0236 AC: 2034 AN: 86232

European-Finnish (FIN) AF: 0.0188 AC: 1002 AN: 53406

Middle Eastern (MID) AF: 0.0187 AC: 108 AN: 5768

European-Non Finnish (NFE) AF: 0.0213 AC: 23668 AN: 1111134

Other (OTH) AF: 0.0222 AC: 1338 AN: 60358

GnomAD4 genome AF: 0.0209 AC: 3180 AN: 152222 Hom.: 69 Cov.: 32 AF XY: 0.0219 AC XY: 1627 AN XY: 74426

African (AFR) AF: 0.00549 AC: 228 AN: 41532

American (AMR) AF: 0.0748 AC: 1143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4830

European-Finnish (FIN) AF: 0.0176 AC: 186 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0202 AC: 1376 AN: 68012

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.0217 Hom.: 144

Bravo AF: 0.0263

EpiCase AF: 0.0204

EpiControl AF: 0.0187

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	FUT8-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.8
DANN	Benign	0.67
PhyloP100		2.3
Mutation Taster		=97/3	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: rs35137471; hg19: chr14-66096297;