Genetic Variant NM_024709.5:c.170A>T (chr1-220690572-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024709.5(C1orf115):c.170A>T(p.Asp57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000878 in 1,490,266 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

C1orf115
NM_024709.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.599

Publications

2 publications found

Variant links:

Genes affected

C1orf115 (HGNC:25873): (chromosome 1 open reading frame 115) Located in 9+0 non-motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

C1orf115 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035063326).

BP6

Variant 1-220690572-A-T is Benign according to our data. Variant chr1-220690572-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2247474.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024709.5. 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
	C1orf115	NM_024709.5	MANE Select	c.170A>T	p.Asp57Val	missense	Exon 1 of 2	NP_078985.3	Q9H7X2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf115	ENST00000294889.6	TSL:1 MANE Select	c.170A>T	p.Asp57Val	missense	Exon 1 of 2	ENSP00000294889.5	Q9H7X2

Frequencies

GnomAD3 genomes

AF:

0.000817

AC:

124

AN:

151794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00433

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:

0.000648

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000567

AC:

AN:

84664

AF XY:

0.000508

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000534

Gnomad OTH exome

AF:

0.000873

GnomAD4 exome

AF:

0.000885

AC:

1184

AN:

1338360

Hom.:

Cov.:

AF XY:

0.000864

AC XY:

569

AN XY:

658834

show subpopulations

African (AFR)

AF:

0.000113

AC:

AN:

26454

American (AMR)

AF:

0.00249

AC:

AN:

26100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21798

East Asian (EAS)

AF:

0.00

AC:

AN:

30436

South Asian (SAS)

AF:

0.0000558

AC:

AN:

71694

European-Finnish (FIN)

AF:

0.0000428

AC:

AN:

46714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3984

European-Non Finnish (NFE)

AF:

0.00101

AC:

1067

AN:

1056008

Other (OTH)

AF:

0.000779

AC:

AN:

55172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

163

245

326

408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.000816

AC:

124

AN:

151906

Hom.:

Cov.:

AF XY:

0.000875

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41462

American (AMR)

AF:

0.00433

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000648

AC:

AN:

67898

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000115

Hom.:

Bravo

AF:

0.00114

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.9

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.043

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.60

PROVEAN

Benign

-0.77

REVEL

Benign

0.020

Sift

Benign

0.28

Sift4G

Benign

0.13

Polyphen

0.36

Vest4

0.12

MVP

0.030

MPC

0.57

ClinPred

0.0092

GERP RS

-3.1

PromoterAI

-0.0075

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.095

gMVP

0.10

Mutation Taster

=92/8

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

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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