Variant 2-182837942-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001463.4(FRZB):c.861+6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,608,016 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 26 hom. )

Consequence

FRZB
NM_001463.4 splice_region, intron

Scores

Splicing: ADA: 0.0001893

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.312

Variant links:

Genes affected

FRZB (HGNC:3959): (frizzled related protein) The protein encoded by this gene is a secreted protein that is involved in the regulation of bone development. Defects in this gene are a cause of female-specific osteoarthritis (OA) susceptibility. [provided by RefSeq, Apr 2010]

FRZB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-182837942-G-T is Benign according to our data. Variant chr2-182837942-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 719233.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 446 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRZB	NM_001463.4 linkuse as main transcript	c.861+6C>A		splice_region_variant, intron_variant		ENST00000295113.5	NP_001454.2	Q92765D9ZGF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRZB	ENST00000295113.5 linkuse as main transcript	c.861+6C>A		splice_region_variant, intron_variant		1	NM_001463.4	ENSP00000295113.4		Q92765

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

446

AN:

151670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00336

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000663

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00502

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00285

AC:

714

AN:

250270

Hom.:

AF XY:

0.00299

AC XY:

405

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.00340

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000746

Gnomad NFE exome

AF:

0.00487

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00478

AC:

6955

AN:

1456228

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

3360

AN XY:

724610

show subpopulations

Gnomad4 AFR exome

AF:

0.000781

Gnomad4 AMR exome

AF:

0.00332

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000697

Gnomad4 NFE exome

AF:

0.00587

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.00294

AC:

446

AN:

151788

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

217

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00335

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000663

Gnomad4 NFE

AF:

0.00502

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00361

Hom.:

Bravo

AF:

0.00328

EpiCase

AF:

0.00377

EpiControl

AF:

0.00522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.038

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