rs740223

chr22-30366151-G-Achr22-30366151-G-C

Variant summary

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

The NM_001017437.5(CCDC157):c.151G>A(p.Asp51Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,613,584 control chromosomes in the GnomAD database, including 41,813 homozygotes. In-silico tool predicts 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 0.20 (3366 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38447 hom.)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.17

Genes affected

CCDC157 (HGNC:33854): (coiled-coil domain containing 157)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016170144).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC157	NM_001017437.5	c.151G>A	p.Asp51Asn	missense_variant	3/12	ENST00000338306.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC157	ENST00000338306.8	c.151G>A	p.Asp51Asn	missense_variant	3/12	5	NM_001017437.5	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30703 AN: 152104 Hom.: 3366 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0960

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.197 AC: 49350 AN: 250802 Hom.: 5432 AF XY: 0.199 AC XY: 26990 AN XY: 135640

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.246

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.224 AC: 326929 AN: 1461362 Hom.: 38447 Cov.: 35 AF XY: 0.221 AC XY: 160937 AN XY: 727028

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.202 AC: 30704 AN: 152222 Hom.: 3366 Cov.: 32 AF XY: 0.195 AC XY: 14509 AN XY: 74440

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.244

Alfa AF: 0.239 Hom.: 5955

Bravo AF: 0.207

TwinsUK AF: 0.234 AC: 866

ALSPAC AF: 0.252 AC: 971

ESP6500AA AF: 0.151 AC: 667

ESP6500EA AF: 0.256 AC: 2204

ExAC AF: 0.196 AC: 23796

Asia WGS AF: 0.130 AC: 455 AN: 3478

EpiCase AF: 0.265

EpiControl AF: 0.272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.10	T;T;T;T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;.;D;D;D
MetaRNN	Benign	0.0016	T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	0.00095	P;P;P
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.6	D;N;N;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Uncertain	0.045	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.79
MPC		0.46
ClinPred		0.010	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.45

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: rs740223; hg19: chr22-30762140; COSMIC: COSV57837547; COSMIC: COSV57837547;