22-30375469-T-C

Position:

• chr22-30375469-T-C

Variant summary

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

The NM_001017437.5(CCDC157):​c.1673-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,613,174 control chromosomes in the GnomAD database, including 41,915 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.

• Frequency:
  • Genomes: 𝑓 0.20 (3389 hom., cov: 31)
  • Exomes 𝑓: 0.22 (38526 hom.)
• Consequence: CCDC157 NM_001017437.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

Genes affected

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

KIAA1656 (HGNC:):

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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.1673-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000338306.8
KIAA1656	NR_046312.1	n.947A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC157	ENST00000338306.8	c.1673-10T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001017437.5	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30857 AN: 152050 Hom.: 3389 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.197 AC: 49475 AN: 250944 Hom.: 5442 AF XY: 0.199 AC XY: 27014 AN XY: 135642

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.224 AC: 327147 AN: 1461008 Hom.: 38526 Cov.: 31 AF XY: 0.222 AC XY: 161005 AN XY: 726828

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.148

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: 0.228

GnomAD4 genome AF: 0.203 AC: 30857 AN: 152166 Hom.: 3389 Cov.: 31 AF XY: 0.196 AC XY: 14572 AN XY: 74398

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0951

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.245

Alfa AF: 0.238 Hom.: 6448

Bravo AF: 0.208

Asia WGS AF: 0.130 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.031
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 10

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

Publications

LitVar

Other links and lift over

dbSNP: rs1002189; hg19: chr22-30771458; COSMIC: COSV53175799; COSMIC: COSV53175799;