Genetic Variant 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

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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