Variant 2-158340336-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_138803.4(CCDC148):c.392A>G(p.Gln131Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,986 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

CCDC148
NM_138803.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.650

Variant links:

Genes affected

CCDC148 (HGNC:25191): (coiled-coil domain containing 148)

CCDC148 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008282959).

BP6

Variant 2-158340336-T-C is Benign according to our data. Variant chr2-158340336-T-C is described in ClinVar as [Benign]. Clinvar id is 724325.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC148	NM_138803.4 linkuse as main transcript	c.392A>G	p.Gln131Arg	missense_variant	5/14	ENST00000283233.10
CCDC148	NM_001301685.2 linkuse as main transcript	c.392A>G	p.Gln131Arg	missense_variant	5/7
CCDC148	NM_001301684.2 linkuse as main transcript	c.48+262A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC148	ENST00000283233.10 linkuse as main transcript	c.392A>G	p.Gln131Arg	missense_variant	5/14	1	NM_138803.4		Q8NFR7-1

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000832

AC:

209

AN:

251312

Hom.:

AF XY:

0.000707

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000356

AC:

521

AN:

1461650

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

228

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.00312

AC:

476

AN:

152336

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000598

Hom.:

Bravo

AF:

0.00322

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000923

AC:

112

Asia WGS

AF:

0.000867

AC:

AN:

3474

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.61

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.23

B;.;.

Vest4

0.20

MVP

0.24

MPC

0.039

ClinPred

0.026

GERP RS

-0.10

Varity_R

0.10

gMVP

0.070

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