22-30375469-T-C

Variant names:

• chr22-30375469-T-C
• rs1002189
• NM_001017437.5:c.1673-10T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017437.5(CCDC157):​c.1673-10T>C variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 18 publications found

Genes affected

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

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]

KIAA1656 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017437.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC157	NM_001017437.5	MANE Select	c.1673-10T>C		intron	N/A	NP_001017437.3	Q569K6
	CCDC157	NM_001318334.2		c.1673-10T>C		intron	N/A	NP_001305263.2	Q569K6
	KIAA1656	NR_046312.1		n.947A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC157	ENST00000338306.8	TSL:5 MANE Select	c.1673-10T>C		intron	N/A	ENSP00000343087.3	Q569K6
	CCDC157	ENST00000405659.5	TSL:1	c.1673-10T>C		intron	N/A	ENSP00000385357.1	Q569K6
	CCDC157	ENST00000943832.1		c.758-10T>C		intron	N/A	ENSP00000613891.1

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

GnomAD2 exomes AF: 0.197 AC: 49475 AN: 250944 AF XY: 0.199

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 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

African (AFR) AF: 0.156 AC: 5228 AN: 33462

American (AMR) AF: 0.148 AC: 6602 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 8261 AN: 26124

East Asian (EAS) AF: 0.109 AC: 4323 AN: 39684

South Asian (SAS) AF: 0.110 AC: 9481 AN: 86236

European-Finnish (FIN) AF: 0.160 AC: 8552 AN: 53306

Middle Eastern (MID) AF: 0.266 AC: 1535 AN: 5764

European-Non Finnish (NFE) AF: 0.242 AC: 269422 AN: 1111378

Other (OTH) AF: 0.228 AC: 13743 AN: 60354

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

African (AFR) AF: 0.155 AC: 6446 AN: 41506

American (AMR) AF: 0.210 AC: 3218 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1111 AN: 3472

East Asian (EAS) AF: 0.134 AC: 693 AN: 5168

South Asian (SAS) AF: 0.0951 AC: 459 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10598

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16486 AN: 67984

Other (OTH) AF: 0.245 AC: 515 AN: 2106

Alfa AF: 0.232 Hom.: 15128

Bravo AF: 0.208

Asia WGS AF: 0.130 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.031
DANN	Benign	0.50
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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