11-22859456-C-T

Variant names:

• chr11-22859456-C-T
• rs3213706
• NM_001195637.2:c.86G>A

Variant summary

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

The NM_001195637.2(CCDC179):​c.86G>A​(p.Arg29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,480,584 control chromosomes in the GnomAD database, including 106,318 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.37 (10714 hom., cov: 32)
  • Exomes 𝑓: 0.37 (95604 hom.)
• Consequence: CCDC179 NM_001195637.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 18 publications found

Genes affected

CCDC179 (HGNC:44653): (coiled-coil domain containing 179)

ENSG00000246225 (HGNC:):

LINC02718 (HGNC:54235): (long intergenic non-protein coding RNA 2718)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=6.5648514E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC179	NM_001195637.2	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 4	ENST00000532798.3	NP_001182566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC179	ENST00000532798.3	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 4	2	NM_001195637.2	ENSP00000457511.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55548 AN: 151782 Hom.: 10709 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.401

GnomAD2 exomes AF: 0.402 AC: 49259 AN: 122536 AF XY: 0.409

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.630

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.371 AC: 493124 AN: 1328684 Hom.: 95604 Cov.: 28 AF XY: 0.375 AC XY: 245265 AN XY: 654066

African (AFR) AF: 0.325 AC: 9926 AN: 30572

American (AMR) AF: 0.411 AC: 13529 AN: 32904

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 8698 AN: 23868

East Asian (EAS) AF: 0.657 AC: 22568 AN: 34324

South Asian (SAS) AF: 0.519 AC: 35003 AN: 67504

European-Finnish (FIN) AF: 0.259 AC: 8277 AN: 31966

Middle Eastern (MID) AF: 0.483 AC: 2599 AN: 5386

European-Non Finnish (NFE) AF: 0.354 AC: 371060 AN: 1046920

Other (OTH) AF: 0.389 AC: 21464 AN: 55240

GnomAD4 genome AF: 0.366 AC: 55581 AN: 151900 Hom.: 10714 Cov.: 32 AF XY: 0.369 AC XY: 27414 AN XY: 74258

African (AFR) AF: 0.328 AC: 13597 AN: 41416

American (AMR) AF: 0.433 AC: 6618 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3472

East Asian (EAS) AF: 0.644 AC: 3315 AN: 5148

South Asian (SAS) AF: 0.564 AC: 2711 AN: 4804

European-Finnish (FIN) AF: 0.253 AC: 2659 AN: 10530

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24132 AN: 67936

Other (OTH) AF: 0.398 AC: 842 AN: 2114

Alfa AF: 0.373 Hom.: 36642

Bravo AF: 0.374

TwinsUK AF: 0.366 AC: 1358

ALSPAC AF: 0.357 AC: 1375

ExAC AF: 0.439 AC: 6209

Asia WGS AF: 0.578 AC: 2006 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.8
DANN	Benign	0.71
DEOGEN2	Benign	0.052	T
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0000066	T
PhyloP100		-1.0
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.1	D
Sift	Benign	0.059	T
Sift4G	Pathogenic	0.0	D
Vest4		0.061
GERP RS		-3.0
Varity_R		0.048
gMVP		0.021
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: rs3213706; hg19: chr11-22881002; COSMIC: COSV72299344; COSMIC: COSV72299344;