dbSNP rs1129942: C1orf105:p.Ser137Asn (chr1-172468452-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139240.4(C1orf105):c.410G>A(p.Ser137Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,608,462 control chromosomes in the GnomAD database, including 510,662 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.78 ( 46506 hom., cov: 32)

Exomes 𝑓: 0.80 ( 464156 hom. )

Consequence

C1orf105
NM_139240.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.313

Publications

27 publications found

Variant links:

Genes affected

C1orf105 (HGNC:29591): (chromosome 1 open reading frame 105)

C1orf105 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=8.3782754E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf105	NM_139240.4 link	c.410G>A	p.Ser137Asn	missense_variant	Exon 7 of 7	ENST00000367727.9	NP_640333.3	O95561

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C1orf105	ENST00000367727.9 link	c.410G>A	p.Ser137Asn	missense_variant	Exon 7 of 7	1	NM_139240.4	ENSP00000356700.4	O95561
C1orf105	ENST00000367725.4 link	c.380G>A	p.Ser127Asn	missense_variant	Exon 5 of 5	2		ENSP00000356698.4	Q5R3C7
C1orf105	ENST00000367726.1 link	n.214G>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

118472

AN:

152008

Hom.:

46486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.896

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.910

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.814

GnomAD2 exomes

AF:

0.827

AC:

206356

AN:

249618

AF XY:

0.830

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.792

Gnomad OTH exome

AF:

0.835

GnomAD4 exome

AF:

0.796

AC:

1159462

AN:

1456336

Hom.:

464156

Cov.:

AF XY:

0.800

AC XY:

579713

AN XY:

724598

show subpopulations

African (AFR)

AF:

0.701

AC:

23332

AN:

33282

American (AMR)

AF:

0.873

AC:

38650

AN:

44264

Ashkenazi Jewish (ASJ)

AF:

0.890

AC:

23056

AN:

25892

East Asian (EAS)

AF:

0.999

AC:

39635

AN:

39668

South Asian (SAS)

AF:

0.897

AC:

76905

AN:

85706

European-Finnish (FIN)

AF:

0.740

AC:

39434

AN:

53272

Middle Eastern (MID)

AF:

0.888

AC:

5093

AN:

5736

European-Non Finnish (NFE)

AF:

0.780

AC:

864638

AN:

1108360

Other (OTH)

AF:

0.810

AC:

48719

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10470

20940

31411

41881

52351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20600

41200

61800

82400

103000

<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:

0.779

AC:

118546

AN:

152126

Hom.:

46506

Cov.:

AF XY:

0.782

AC XY:

58168

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.703

AC:

29139

AN:

41472

American (AMR)

AF:

0.848

AC:

12966

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.896

AC:

3110

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5178

AN:

5186

South Asian (SAS)

AF:

0.909

AC:

4381

AN:

4818

European-Finnish (FIN)

AF:

0.732

AC:

7739

AN:

10572

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.784

AC:

53297

AN:

68000

Other (OTH)

AF:

0.816

AC:

1723

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1337

2674

4010

5347

6684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.794

Hom.:

118893

Bravo

AF:

0.786

TwinsUK

AF:

0.774

AC:

2871

ALSPAC

AF:

0.782

AC:

3015

ESP6500AA

AF:

0.708

AC:

3120

ESP6500EA

AF:

0.785

AC:

6750

ExAC

AF:

0.825

AC:

100142

Asia WGS

AF:

0.936

AC:

3256

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0055

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

8.4e-7

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

PhyloP100

-0.31

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.061

Sift

Benign

0.32

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.040

B;.

Vest4

0.040

MPC

0.11

ClinPred

0.0042

GERP RS

1.1

Varity_R

0.049

gMVP

0.020

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over