Genetic Variant C1orf159:c.311-23T>C (chr1-1086035-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017891.5(C1orf159):c.311-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,610,786 control chromosomes in the GnomAD database, including 438,884 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 43689 hom., cov: 36)

Exomes 𝑓: 0.73 ( 395195 hom. )

Consequence

C1orf159
NM_017891.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

15 publications found

Variant links:

Genes affected

C1orf159 (HGNC:26062): (chromosome 1 open reading frame 159) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1orf159 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
C1orf159	NM_017891.5 link	c.311-23T>C	intron_variant	Intron 6 of 9	ENST00000421241.7	NP_060361.4	Q96HA4-4A0A024R082
C1orf159	NM_001330306.2 link	c.419-23T>C	intron_variant	Intron 8 of 11		NP_001317235.1	Q96HA4-1
C1orf159	NM_001363525.2 link	c.311-23T>C	intron_variant	Intron 7 of 10		NP_001350454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf159	ENST00000421241.7 link	c.311-23T>C		intron_variant	Intron 6 of 9	2	NM_017891.5	ENSP00000400736.2		Q96HA4-4

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114937

AN:

152172

Hom.:

43652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.795

Gnomad ASJ

AF:

0.811

Gnomad EAS

AF:

0.897

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.767

GnomAD2 exomes

AF:

0.762

AC:

188000

AN:

246568

AF XY:

0.760

show subpopulations

Gnomad AFR exome

AF:

0.786

Gnomad AMR exome

AF:

0.823

Gnomad ASJ exome

AF:

0.797

Gnomad EAS exome

AF:

0.895

Gnomad FIN exome

AF:

0.730

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.756

GnomAD4 exome

AF:

0.735

AC:

1071693

AN:

1458496

Hom.:

395195

Cov.:

AF XY:

0.736

AC XY:

533574

AN XY:

725396

show subpopulations

African (AFR)

AF:

0.780

AC:

26107

AN:

33450

American (AMR)

AF:

0.821

AC:

36606

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.797

AC:

20798

AN:

26084

East Asian (EAS)

AF:

0.910

AC:

36102

AN:

39662

South Asian (SAS)

AF:

0.781

AC:

67252

AN:

86142

European-Finnish (FIN)

AF:

0.729

AC:

37777

AN:

51824

Middle Eastern (MID)

AF:

0.775

AC:

4325

AN:

5580

European-Non Finnish (NFE)

AF:

0.718

AC:

797666

AN:

1110912

Other (OTH)

AF:

0.748

AC:

45060

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14070

28141

42211

56282

70352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20032

40064

60096

80128

100160

<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:

0.755

AC:

115038

AN:

152290

Hom.:

43689

Cov.:

AF XY:

0.759

AC XY:

56506

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.784

AC:

32590

AN:

41552

American (AMR)

AF:

0.795

AC:

12163

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

2815

AN:

3470

East Asian (EAS)

AF:

0.897

AC:

4645

AN:

5180

South Asian (SAS)

AF:

0.781

AC:

3775

AN:

4834

European-Finnish (FIN)

AF:

0.732

AC:

7774

AN:

10624

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.717

AC:

48746

AN:

68006

Other (OTH)

AF:

0.768

AC:

1621

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1532

3064

4596

6128

7660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.730

Hom.:

61217

Bravo

AF:

0.760

Asia WGS

AF:

0.840

AC:

2922

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.0

(source)

DANN

Benign

0.33

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over