rs2074422

Variant names:

• chr11-60842499-A-G
• rs2074422
• NM_024098.4:c.375A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024098.4(CCDC86):​c.375A>G​(p.Pro125Pro) 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
• Publications: 17 publications found

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]

ENSG00000255959 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024098.4. 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
	CCDC86	NM_024098.4	MANE Select	c.375A>G	p.Pro125Pro	synonymous	Exon 1 of 4	NP_077003.1
	CCDC86-AS1	NR_182293.1		n.317-519T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC86	ENST00000227520.10	TSL:1 MANE Select	c.375A>G	p.Pro125Pro	synonymous	Exon 1 of 4	ENSP00000227520.5
	ENSG00000255959	ENST00000753860.1		n.162T>C		non_coding_transcript_exon	Exon 1 of 2
	CCDC86	ENST00000535217.1	TSL:5	n.259+95A>G		intron	N/A	ENSP00000442111.1

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

GnomAD2 exomes AF: 0.185 AC: 46378 AN: 250336 AF XY: 0.190

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 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

African (AFR) AF: 0.180 AC: 6019 AN: 33476

American (AMR) AF: 0.123 AC: 5496 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7782 AN: 26134

East Asian (EAS) AF: 0.127 AC: 5035 AN: 39700

South Asian (SAS) AF: 0.219 AC: 18872 AN: 86258

European-Finnish (FIN) AF: 0.124 AC: 6595 AN: 53182

Middle Eastern (MID) AF: 0.258 AC: 1490 AN: 5768

European-Non Finnish (NFE) AF: 0.216 AC: 240528 AN: 1112008

Other (OTH) AF: 0.214 AC: 12909 AN: 60390

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

African (AFR) AF: 0.180 AC: 7480 AN: 41508

American (AMR) AF: 0.159 AC: 2437 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3466

East Asian (EAS) AF: 0.117 AC: 602 AN: 5166

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4822

European-Finnish (FIN) AF: 0.115 AC: 1220 AN: 10606

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14786 AN: 67966

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.208 Hom.: 2636

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.53
PhyloP100		-1.6
PromoterAI		0.045	Neutral
Mutation Taster		=100/0	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: rs2074422; hg19: chr11-60609972; COSMIC: COSV57125952; COSMIC: COSV57125952;