Genetic Variant CCDC180:p.Arg40His (chr9-97309463-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020893.6(CCDC180):c.119G>A(p.Arg40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,605,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R40P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

CCDC180
NM_020893.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

0 publications found

Variant links:

Genes affected

CCDC180 (HGNC:29303): (coiled-coil domain containing 180) The protein encoded by this gene contains a coiled-coil domain. Alternative splicing results in multiple transcript variants encoding different isoforms. A single nucleotide polymorphism (SNP) in this gene has been associated with increased susceptibility to Behcet's Disease (PMID: 19442274). [provided by RefSeq, Dec 2016]

CCDC180 links:

SUGT1P4-STRA6LP-CCDC180 (HGNC:53835): (SUGT1P4-STRA6LP-CCDC180 readthrough) This locus represents a set of read-through transcripts spanning an upstream pseudogene (GeneID:100499484) extending into a downstream protein-coding locus (GeneID:100499483). All of the read-through transcripts are candidates for nonsense-mediated decay (NMD), so they are not thought to express a protein. [provided by RefSeq, Aug 2010]

SUGT1P4-STRA6LP-CCDC180 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028869152).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020893.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC180	NM_020893.6	MANE Select	c.119G>A	p.Arg40His	missense	Exon 3 of 37	NP_065944.3	A0A6E1Y6F7
CCDC180	NM_001348010.4		c.119G>A	p.Arg40His	missense	Exon 4 of 21	NP_001334939.2
SUGT1P4-STRA6LP-CCDC180	NR_036527.1		n.1674G>A		non_coding_transcript_exon	Exon 17 of 49

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC180	ENST00000529487.3	TSL:1 MANE Select	c.119G>A	p.Arg40His	missense	Exon 3 of 37	ENSP00000434727.2	A0A6E1Y6F7
CCDC180	ENST00000494917.6	TSL:1	n.322G>A		non_coding_transcript_exon	Exon 4 of 20
CCDC180	ENST00000867263.1		c.119G>A	p.Arg40His	missense	Exon 4 of 35	ENSP00000537322.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000825

AC:

AN:

242450

AF XY:

0.00000762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000385

AC:

AN:

1453392

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

722786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33012

American (AMR)

AF:

0.0000461

AC:

AN:

43422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25940

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38904

South Asian (SAS)

AF:

0.00

AC:

AN:

84668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000406

AC:

AN:

1108274

Other (OTH)

AF:

0.000133

AC:

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000943

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.72

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.31

M_CAP

Benign

0.0036

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.99

PhyloP100

-0.15

PrimateAI

Benign

0.25

PROVEAN

Benign

0.89

REVEL

Benign

0.021

Sift

Benign

0.69

Sift4G

Benign

0.40

Vest4

0.10

MVP

0.030

ClinPred

0.012

GERP RS

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.047

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over