Variant 20-32216732-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000375749.8(POFUT1):c.542+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,578,646 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 28 hom., cov: 32)

Exomes 𝑓: 0.019 ( 302 hom. )

Consequence

POFUT1
ENST00000375749.8 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

POFUT1 (HGNC:14988): (protein O-fucosyltransferase 1) This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

POFUT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 20-32216732-G-C is Benign according to our data. Variant chr20-32216732-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1170434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2156/152266) while in subpopulation NFE AF= 0.02 (1357/68018). AF 95% confidence interval is 0.0191. There are 28 homozygotes in gnomad4. There are 1108 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2156 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
POFUT1	NM_015352.2 linkuse as main transcript	c.542+11G>C	intron_variant	ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2 linkuse as main transcript	c.542+11G>C	intron_variant		NP_758436.1
POFUT1	XM_047440079.1 linkuse as main transcript	c.218+11G>C	intron_variant		XP_047296035.1
POFUT1	XR_007067447.1 linkuse as main transcript	n.604+11G>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8 linkuse as main transcript	c.542+11G>C		intron_variant		1	NM_015352.2	ENSP00000364902	P1	Q9H488-1

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2156

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0144

AC:

3612

AN:

251064

Hom.:

AF XY:

0.0144

AC XY:

1959

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.00571

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.0413

Gnomad NFE exome

AF:

0.0203

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0188

AC:

26881

AN:

1426380

Hom.:

302

Cov.:

AF XY:

0.0183

AC XY:

13022

AN XY:

711792

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.00580

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00141

Gnomad4 FIN exome

AF:

0.0409

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0142

AC:

2156

AN:

152266

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1108

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00438

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0409

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00692

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2019	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dowling-Degos disease 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.0

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over