22-28786512-C-A

Variant names:

• chr22-28786512-C-A
• rs5762795
• NM_173510.4:c.*186C>A

Variant summary

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

The NM_173510.4(CCDC117):​c.*186C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 551,592 control chromosomes in the GnomAD database, including 46,522 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 0.43 (15906 hom., cov: 32)
  • Exomes 𝑓: 0.37 (30616 hom.)
• Consequence: CCDC117 NM_173510.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 28 publications found

Genes affected

CCDC117 (HGNC:26599): (coiled-coil domain containing 117)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC117	NM_173510.4	c.*186C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000249064.9	NP_775781.1
CCDC117	NM_001284263.2	c.*186C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001271192.1
CCDC117	NM_001284264.2	c.*186C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001271193.1
CCDC117	NM_001284265.1	c.*186C>A		3_prime_UTR_variant	Exon 5 of 5		NP_001271194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC117	ENST00000249064.9	c.*186C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_173510.4	ENSP00000249064.4
CCDC117	ENST00000448492.6	c.*186C>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000389478.2
CCDC117	ENST00000421503.6	c.*186C>A		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000387827.2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64823 AN: 151770 Hom.: 15857 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.372 AC: 148782 AN: 399704 Hom.: 30616 Cov.: 4 AF XY: 0.377 AC XY: 78822 AN XY: 209352

African (AFR) AF: 0.653 AC: 7594 AN: 11624

American (AMR) AF: 0.325 AC: 4420 AN: 13582

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 3933 AN: 12646

East Asian (EAS) AF: 0.678 AC: 19494 AN: 28750

South Asian (SAS) AF: 0.504 AC: 18023 AN: 35760

European-Finnish (FIN) AF: 0.377 AC: 10007 AN: 26534

Middle Eastern (MID) AF: 0.385 AC: 693 AN: 1802

European-Non Finnish (NFE) AF: 0.309 AC: 75845 AN: 245550

Other (OTH) AF: 0.374 AC: 8773 AN: 23456

GnomAD4 genome AF: 0.428 AC: 64936 AN: 151888 Hom.: 15906 Cov.: 32 AF XY: 0.430 AC XY: 31890 AN XY: 74210

African (AFR) AF: 0.652 AC: 27019 AN: 41420

American (AMR) AF: 0.310 AC: 4735 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1145 AN: 3460

East Asian (EAS) AF: 0.676 AC: 3496 AN: 5174

South Asian (SAS) AF: 0.537 AC: 2583 AN: 4810

European-Finnish (FIN) AF: 0.375 AC: 3935 AN: 10506

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

European-Non Finnish (NFE) AF: 0.308 AC: 20913 AN: 67938

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.345 Hom.: 28919

Bravo AF: 0.429

Asia WGS AF: 0.616 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.61
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5762795; hg19: chr22-29182500; COSMIC: COSV50771760; COSMIC: COSV50771760;