Variant 4-6288867-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006005.3(WFS1):c.316-120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,455,408 control chromosomes in the GnomAD database, including 291,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33393 hom., cov: 34)

Exomes 𝑓: 0.62 ( 257944 hom. )

Consequence

WFS1
NM_006005.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.73

Variant links:

Genes affected

WFS1 (HGNC:12762): (wolframin ER transmembrane glycoprotein) This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease affects the brain and central nervous system. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]

WFS1 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=-0.95).

BP6

Variant 4-6288867-T-C is Benign according to our data. Variant chr4-6288867-T-C is described in ClinVar as [Benign]. Clinvar id is 1292284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFS1	NM_006005.3 link	c.316-120T>C		intron_variant		ENST00000226760.5	NP_005996.2	O76024A0A0S2Z4V6
WFS1	NM_001145853.1 link	c.316-120T>C		intron_variant			NP_001139325.1	O76024A0A0S2Z4V6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFS1	ENST00000226760.5 link	c.316-120T>C		intron_variant		1	NM_006005.3	ENSP00000226760.1		O76024

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99615

AN:

152000

Hom.:

33350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.942

Gnomad SAS

AF:

0.710

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.625

AC:

814156

AN:

1303290

Hom.:

257944

Cov.:

AF XY:

0.627

AC XY:

405918

AN XY:

647812

show subpopulations

Gnomad4 AFR exome

AF:

0.715

Gnomad4 AMR exome

AF:

0.742

Gnomad4 ASJ exome

AF:

0.694

Gnomad4 EAS exome

AF:

0.965

Gnomad4 SAS exome

AF:

0.700

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.654

GnomAD4 genome

AF:

0.656

AC:

99717

AN:

152118

Hom.:

33393

Cov.:

AF XY:

0.658

AC XY:

48909

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.707

Gnomad4 AMR

AF:

0.707

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.943

Gnomad4 SAS

AF:

0.710

Gnomad4 FIN

AF:

0.574

Gnomad4 NFE

AF:

0.601

Gnomad4 OTH

AF:

0.672

Alfa

AF:

0.622

Hom.:

3506

Bravo

AF:

0.668

Asia WGS

AF:

0.825

AC:

2869

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.40

DANN

Benign

0.52

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

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