Variant 2-158309623-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000283233.10(CCDC148):c.920A>T(p.Tyr307Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,612,286 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 30 hom. )

Consequence

CCDC148
ENST00000283233.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.30

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037602186).

BP6

Variant 2-158309623-T-A is Benign according to our data. Variant chr2-158309623-T-A is described in ClinVar as [Benign]. Clinvar id is 774597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00373 (568/152364) while in subpopulation EAS AF= 0.0262 (136/5186). AF 95% confidence interval is 0.0226. There are 2 homozygotes in gnomad4. There are 282 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC148	NM_138803.4 linkuse as main transcript	c.920A>T	p.Tyr307Phe	missense_variant	9/14	ENST00000283233.10	NP_620158.3
CCDC148	NM_001301684.2 linkuse as main transcript	c.482A>T	p.Tyr161Phe	missense_variant	7/12		NP_001288613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC148	ENST00000283233.10 linkuse as main transcript	c.920A>T	p.Tyr307Phe	missense_variant	9/14	1	NM_138803.4	ENSP00000283233		Q8NFR7-1

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

569

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00428

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00540

AC:

1351

AN:

250402

Hom.:

AF XY:

0.00539

AC XY:

729

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.0323

Gnomad SAS exome

AF:

0.00218

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.00442

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00432

AC:

6304

AN:

1459922

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3094

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.000898

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.00208

Gnomad4 FIN exome

AF:

0.00425

Gnomad4 NFE exome

AF:

0.00408

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00373

AC:

568

AN:

152364

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

282

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0262

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00428

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00453

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00522

AC:

634

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00451

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0034

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.097

Sift

Benign

0.42

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.93

P;P

Vest4

0.39

MVP

0.099

MPC

0.057

ClinPred

0.046

GERP RS

4.8

Varity_R

0.087

gMVP

0.15

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