22-30378351-A-G

Variant names:

• chr22-30378351-A-G
• rs9619104
• NM_001017437.5:c.*1606A>G

Variant summary

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

The NM_001017437.5(CCDC157):​c.*1606A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 290,910 control chromosomes in the GnomAD database, including 109,845 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 0.88 (58719 hom., cov: 33)
  • Exomes 𝑓: 0.86 (51126 hom.)
• Consequence: CCDC157 NM_001017437.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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.*1606A>G		3_prime_UTR	Exon 12 of 12	NP_001017437.3	Q569K6
	CCDC157	NM_001318334.2		c.*1606A>G		3_prime_UTR	Exon 12 of 12	NP_001305263.2	Q569K6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC157	ENST00000338306.8	TSL:5 MANE Select	c.*1606A>G		3_prime_UTR	Exon 12 of 12	ENSP00000343087.3	Q569K6
	RNF215	ENST00000421022.1	TSL:2	c.65-209T>C		intron	N/A	ENSP00000396278.1	H7C0R1
	CCDC157	ENST00000475975.5	TSL:2	n.4482A>G		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133201 AN: 152152 Hom.: 58661 Cov.: 33

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.879

GnomAD4 exome AF: 0.856 AC: 118717 AN: 138640 Hom.: 51126 Cov.: 0 AF XY: 0.865 AC XY: 66462 AN XY: 76858

African (AFR) AF: 0.976 AC: 4055 AN: 4156

American (AMR) AF: 0.858 AC: 7766 AN: 9056

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 2712 AN: 3044

East Asian (EAS) AF: 0.902 AC: 5481 AN: 6076

South Asian (SAS) AF: 0.926 AC: 26681 AN: 28820

European-Finnish (FIN) AF: 0.872 AC: 5437 AN: 6232

Middle Eastern (MID) AF: 0.955 AC: 1324 AN: 1386

European-Non Finnish (NFE) AF: 0.813 AC: 59628 AN: 73328

Other (OTH) AF: 0.861 AC: 5633 AN: 6542

GnomAD4 genome AF: 0.876 AC: 133316 AN: 152270 Hom.: 58719 Cov.: 33 AF XY: 0.880 AC XY: 65544 AN XY: 74440

African (AFR) AF: 0.967 AC: 40185 AN: 41564

American (AMR) AF: 0.872 AC: 13333 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3098 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4689 AN: 5182

South Asian (SAS) AF: 0.921 AC: 4451 AN: 4832

European-Finnish (FIN) AF: 0.887 AC: 9407 AN: 10600

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55337 AN: 68010

Other (OTH) AF: 0.881 AC: 1860 AN: 2112

Alfa AF: 0.820 Hom.: 3223

Bravo AF: 0.876

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.17
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs9619104; hg19: chr22-30774340;