rs12620556

Positions:

• chr2-158340259-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138803.4(CCDC148):​c.469A>G​(p.Met157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,613,240 control chromosomes in the GnomAD database, including 11,744 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (3482 hom., cov: 32)
  • Exomes 𝑓: 0.090 (8262 hom.)
• Consequence: CCDC148 NM_138803.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010456145).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC148	NM_138803.4	c.469A>G	p.Met157Val	missense_variant	5/14	ENST00000283233.10	NP_620158.3
CCDC148	NM_001301685.2	c.469A>G	p.Met157Val	missense_variant	5/7		NP_001288614.1
CCDC148	NM_001301684.2	c.48+339A>G		intron_variant			NP_001288613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC148	ENST00000283233.10	c.469A>G	p.Met157Val	missense_variant	5/14	1	NM_138803.4	ENSP00000283233

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25725 AN: 152042 Hom.: 3468 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.159

GnomAD3 exomes AF: 0.118 AC: 29678 AN: 250870 Hom.: 2709 AF XY: 0.113 AC XY: 15350 AN XY: 135588

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.0980

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.0995

Gnomad FIN exome AF: 0.0710

Gnomad NFE exome AF: 0.0773

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0897 AC: 131012 AN: 1461080 Hom.: 8262 Cov.: 31 AF XY: 0.0899 AC XY: 65326 AN XY: 726896

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.0970

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0684

Gnomad4 NFE exome AF: 0.0725

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.169 AC: 25785 AN: 152160 Hom.: 3482 Cov.: 32 AF XY: 0.169 AC XY: 12540 AN XY: 74404

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0724

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0986 Hom.: 2827

Bravo AF: 0.183

TwinsUK AF: 0.0779 AC: 289

ALSPAC AF: 0.0752 AC: 290

ESP6500AA AF: 0.376 AC: 1655

ESP6500EA AF: 0.0845 AC: 727

ExAC AF: 0.123 AC: 14963

Asia WGS AF: 0.167 AC: 580 AN: 3474

EpiCase AF: 0.0837

EpiControl AF: 0.0864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.053
DANN	Benign	0.32
DEOGEN2	Benign	0.00037	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.15	T;T;T
MetaRNN	Benign	0.0010	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.3	N;.;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.030	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.010
MPC		0.012
ClinPred		0.00055	T
GERP RS		-2.0
Varity_R		0.030
gMVP		0.077

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

Other links and lift over

dbSNP: rs12620556; hg19: chr2-159196771; COSMIC: COSV51760542;