Variant 4-6270099-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.-6+85T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,706 control chromosomes in the GnomAD database, including 26,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26643 hom., cov: 34)

Exomes 𝑓: 0.58 ( 24 hom. )

Consequence

WFS1
NM_006005.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.596

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 4-6270099-T-C is Benign according to our data. Variant chr4-6270099-T-C is described in ClinVar as [Benign]. Clinvar id is 1292283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFS1	NM_006005.3 link	c.-6+85T>C		intron_variant	Intron 1 of 7	ENST00000226760.5	NP_005996.2	O76024A0A0S2Z4V6
WFS1	NM_001145853.1 link	c.-2+85T>C		intron_variant	Intron 1 of 7		NP_001139325.1	O76024A0A0S2Z4V6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WFS1	ENST00000226760.5 link	c.-6+85T>C		intron_variant	Intron 1 of 7	1	NM_006005.3	ENSP00000226760.1		O76024

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88648

AN:

151480

Hom.:

26620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.662

Gnomad ASJ

AF:

0.666

Gnomad EAS

AF:

0.933

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.619

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.608

GnomAD4 exome

AF:

0.576

AC:

AN:

118

Hom.:

AF XY:

0.563

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.538

GnomAD4 genome

AF:

0.585

AC:

88710

AN:

151588

Hom.:

26643

Cov.:

AF XY:

0.589

AC XY:

43643

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.663

Gnomad4 ASJ

AF:

0.666

Gnomad4 EAS

AF:

0.934

Gnomad4 SAS

AF:

0.670

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.581

Hom.:

3202

Bravo

AF:

0.590

Asia WGS

AF:

0.770

AC:

2669

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 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

-1.0

CADD

Benign

6.8

DANN

Benign

0.32

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