Variant 2-158176586-C-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_138803.4(CCDC148):c.1564G>A(p.Glu522Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000758 in 1,612,118 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 11 hom. )

Consequence

CCDC148
NM_138803.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

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

CCDC148 links:

CCDC148-AS1 (HGNC:44134): (CCDC148 antisense RNA 1)

CCDC148-AS1 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 (MetaRNN=0.003357023).

BP6

Variant 2-158176586-C-T is Benign according to our data. Variant chr2-158176586-C-T is described in ClinVar as [Benign]. Clinvar id is 716761.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC148	NM_138803.4 linkuse as main transcript	c.1564G>A	p.Glu522Lys	missense_variant	13/14	ENST00000283233.10
CCDC148-AS1	NR_038850.1 linkuse as main transcript	n.75-15C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
CCDC148	NM_001301684.2 linkuse as main transcript	c.1126G>A	p.Glu376Lys	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC148	ENST00000283233.10 linkuse as main transcript	c.1564G>A	p.Glu522Lys	missense_variant	13/14	1	NM_138803.4		Q8NFR7-1
CCDC148-AS1	ENST00000412781.2 linkuse as main transcript	n.75-15C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

612

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000981

AC:

245

AN:

249862

Hom.:

AF XY:

0.000763

AC XY:

103

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.000842

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000989

GnomAD4 exome

AF:

0.000416

AC:

608

AN:

1459958

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

265

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.000986

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00404

AC:

614

AN:

152160

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

278

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000815

Hom.:

Bravo

AF:

0.00465

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00134

AC:

163

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

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 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0027

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.054

Sift

Benign

0.17

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.28

B;B

Vest4

0.32

MVP

0.22

MPC

0.057

ClinPred

0.022

GERP RS

5.8

Varity_R

0.18

gMVP

0.20

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