rs2074422

Positions:

• chr11-60842499-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024098.4(CCDC86):​c.375A>G​(p.Pro125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,780 control chromosomes in the GnomAD database, including 35,700 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 0.19 (2845 hom., cov: 33)
  • Exomes 𝑓: 0.21 (32855 hom.)
• Consequence: CCDC86 NM_024098.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

CCDC86 (HGNC:28359): (coiled-coil domain containing 86) Enables RNA binding activity. Located in chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC86-AS1 (HGNC:56314): (CCDC86 antisense RNA 1)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=-1.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC86	NM_024098.4	c.375A>G	p.Pro125=	synonymous_variant	1/4	ENST00000227520.10	NP_077003.1
CCDC86-AS1	NR_182293.1	n.317-519T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC86	ENST00000227520.10	c.375A>G	p.Pro125=	synonymous_variant	1/4	1	NM_024098.4	ENSP00000227520	P1
CCDC86-AS1	ENST00000538705.1	n.317-519T>C		intron_variant, non_coding_transcript_variant		3
	ENST00000539897.1	n.349+118T>C		intron_variant, non_coding_transcript_variant		4
CCDC86	ENST00000535217.1	c.260+95A>G		intron_variant, NMD_transcript_variant		5		ENSP00000442111

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29261 AN: 152022 Hom.: 2843 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.185 AC: 46378 AN: 250336 Hom.: 4672 AF XY: 0.190 AC XY: 25761 AN XY: 135530

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.208 AC: 304726 AN: 1461640 Hom.: 32855 Cov.: 33 AF XY: 0.209 AC XY: 151954 AN XY: 727134

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.192 AC: 29272 AN: 152140 Hom.: 2845 Cov.: 33 AF XY: 0.188 AC XY: 13979 AN XY: 74400

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.197

Alfa AF: 0.211 Hom.: 2129

Bravo AF: 0.194

Asia WGS AF: 0.173 AC: 603 AN: 3478

EpiCase AF: 0.229

EpiControl AF: 0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.53

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: rs2074422; hg19: chr11-60609972; COSMIC: COSV57125952; COSMIC: COSV57125952;