Genetic Variant CCDC148:p.Ala448Thr (chr2-158220623-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138803.4(CCDC148):c.1342G>A(p.Ala448Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,603,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A448S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

CCDC148
NM_138803.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096453756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138803.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCDC148	NM_138803.4	MANE Select	c.1342G>A	p.Ala448Thr	missense	Exon 11 of 14	NP_620158.3
CCDC148	NM_001301684.2		c.904G>A	p.Ala302Thr	missense	Exon 9 of 12	NP_001288613.1
CCDC148-AS1	NR_038850.1		n.355+13006C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC148	ENST00000283233.10	TSL:1 MANE Select	c.1342G>A	p.Ala448Thr	missense	Exon 11 of 14	ENSP00000283233.5	Q8NFR7-1
CCDC148	ENST00000448656.5	TSL:1	n.*933G>A		non_coding_transcript_exon	Exon 9 of 12	ENSP00000415540.1	F8WCV9
CCDC148	ENST00000448656.5	TSL:1	n.*933G>A		3_prime_UTR	Exon 9 of 12	ENSP00000415540.1	F8WCV9

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000116

AC:

AN:

240938

AF XY:

0.000146

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000228

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000451

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000909

AC:

132

AN:

1451730

Hom.:

Cov.:

AF XY:

0.0000984

AC XY:

AN XY:

721840

show subpopulations

African (AFR)

AF:

0.0000610

AC:

AN:

32802

American (AMR)

AF:

0.000118

AC:

AN:

42254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25960

East Asian (EAS)

AF:

0.000204

AC:

AN:

39200

South Asian (SAS)

AF:

0.000323

AC:

AN:

83598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000748

AC:

AN:

1109408

Other (OTH)

AF:

0.000117

AC:

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.000590

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000774

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000988

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

M_CAP

Benign

0.0087

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.7

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Benign

0.055

Sift

Uncertain

0.0080

Sift4G

Benign

0.12

Polyphen

0.87

Vest4

0.31

MVP

0.48

MPC

0.072

ClinPred

0.068

GERP RS

4.6

Varity_R

0.074

gMVP

0.13

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over