Genetic Variant C1orf226:c.318-31G>A (chr1-162383151-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_001085375.2(C1orf226):c.318-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,524,234 control chromosomes in the GnomAD database, including 58,896 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.22 ( 4412 hom., cov: 33)

Exomes 𝑓: 0.28 ( 54484 hom. )

Consequence

C1orf226
NM_001085375.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

14 publications found

Variant links:

Genes affected

C1orf226 (HGNC:34351): (chromosome 1 open reading frame 226)

C1orf226 links:

ENSG00000254706 (HGNC:):

ENSG00000254706 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf226	NM_001085375.2 link	c.318-31G>A		intron_variant	Intron 1 of 1	ENST00000458626.4	NP_001078844.1	A1L170-1
C1orf226	NM_001135240.4 link	c.318-31G>A		intron_variant	Intron 2 of 2		NP_001128712.2	A1L170-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
C1orf226	ENST00000458626.4 link	c.318-31G>A	intron_variant	Intron 1 of 1	1	NM_001085375.2	ENSP00000437071.1	A1L170-1
ENSG00000254706	ENST00000420220.1 link	c.318-31G>A	intron_variant	Intron 3 of 3	5		ENSP00000398035.1	F8W6W0
C1orf226	ENST00000426197.2 link	c.447-31G>A	intron_variant	Intron 2 of 2	2		ENSP00000413150.2	A1L170-2
ENSG00000254706	ENST00000367932.3 link	n.*325-31G>A	intron_variant	Intron 2 of 2	4		ENSP00000356909.3	H7BY61

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34150

AN:

152066

Hom.:

4412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.222

GnomAD2 exomes

AF:

0.255

AC:

46796

AN:

183220

AF XY:

0.263

show subpopulations

Gnomad AFR exome

AF:

0.0926

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.278

AC:

381145

AN:

1372050

Hom.:

54484

Cov.:

AF XY:

0.280

AC XY:

188443

AN XY:

672538

show subpopulations

African (AFR)

AF:

0.0872

AC:

2682

AN:

30764

American (AMR)

AF:

0.219

AC:

6971

AN:

31820

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

5299

AN:

20484

East Asian (EAS)

AF:

0.203

AC:

7874

AN:

38830

South Asian (SAS)

AF:

0.344

AC:

24560

AN:

71402

European-Finnish (FIN)

AF:

0.262

AC:

13146

AN:

50214

Middle Eastern (MID)

AF:

0.237

AC:

1264

AN:

5338

European-Non Finnish (NFE)

AF:

0.285

AC:

304442

AN:

1066720

Other (OTH)

AF:

0.264

AC:

14907

AN:

56478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

12173

24347

36520

48694

60867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10338

20676

31014

41352

51690

<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:

0.224

AC:

34150

AN:

152184

Hom.:

4412

Cov.:

AF XY:

0.224

AC XY:

16656

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0997

AC:

4143

AN:

41536

American (AMR)

AF:

0.239

AC:

3651

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

873

AN:

3468

East Asian (EAS)

AF:

0.204

AC:

1056

AN:

5166

South Asian (SAS)

AF:

0.338

AC:

1630

AN:

4828

European-Finnish (FIN)

AF:

0.248

AC:

2623

AN:

10582

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.285

AC:

19370

AN:

67984

Other (OTH)

AF:

0.221

AC:

467

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1334

2668

4001

5335

6669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.246

Hom.:

1919

Bravo

AF:

0.215

Asia WGS

AF:

0.275

AC:

955

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.77

(source)

DANN

Benign

0.66

PhyloP100

1.6

BranchPoint Hunter

4.0

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