Genetic Variant C1RL:c.*312G>A (chr12-7096079-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016546.4(C1RL):c.*312G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,107,724 control chromosomes in the GnomAD database, including 37,929 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 0.24 ( 4892 hom., cov: 32)

Exomes 𝑓: 0.26 ( 33037 hom. )

Consequence

C1RL
NM_016546.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457

Publications

17 publications found

Variant links:

Genes affected

C1RL (HGNC:21265): (complement C1r subcomponent like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C1RL 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 (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
C1RL	NM_016546.4 link	c.*312G>A	3_prime_UTR_variant	Exon 6 of 6	ENST00000266542.9	NP_057630.2
C1RL	NM_001297640.2 link	c.*312G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001284569.1
C1RL	NM_001297642.2 link	c.*878G>A	3_prime_UTR_variant	Exon 6 of 6		NP_001284571.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
C1RL	ENST00000266542.9 link	c.*312G>A	3_prime_UTR_variant	Exon 6 of 6	1	NM_016546.4	ENSP00000266542.4
C1RL	ENST00000545280.5 link	c.269-2209G>A	intron_variant	Intron 3 of 3	3		ENSP00000438286.1
C1RL	ENST00000504702.2 link	n.33-854G>A	intron_variant	Intron 1 of 1	2
C1RL	ENST00000539803.5 link	n.134-2209G>A	intron_variant	Intron 2 of 6	5		ENSP00000444157.1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37056

AN:

151888

Hom.:

4886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.261

AC:

248999

AN:

955716

Hom.:

33037

Cov.:

AF XY:

0.262

AC XY:

117109

AN XY:

446858

show subpopulations

African (AFR)

AF:

0.159

AC:

3160

AN:

19844

American (AMR)

AF:

0.392

AC:

2182

AN:

5568

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

2967

AN:

9774

East Asian (EAS)

AF:

0.153

AC:

1859

AN:

12118

South Asian (SAS)

AF:

0.335

AC:

7344

AN:

21934

European-Finnish (FIN)

AF:

0.207

AC:

1639

AN:

7918

Middle Eastern (MID)

AF:

0.294

AC:

671

AN:

2286

European-Non Finnish (NFE)

AF:

0.262

AC:

220163

AN:

840798

Other (OTH)

AF:

0.254

AC:

9014

AN:

35476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

8874

17748

26623

35497

44371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9402

18804

28206

37608

47010

<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:

0.244

AC:

37090

AN:

152008

Hom.:

4892

Cov.:

AF XY:

0.242

AC XY:

18011

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.169

AC:

7024

AN:

41444

American (AMR)

AF:

0.367

AC:

5609

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1000

AN:

3466

East Asian (EAS)

AF:

0.182

AC:

940

AN:

5158

South Asian (SAS)

AF:

0.341

AC:

1642

AN:

4816

European-Finnish (FIN)

AF:

0.188

AC:

1989

AN:

10588

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17987

AN:

67944

Other (OTH)

AF:

0.246

AC:

520

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1394

2788

4183

5577

6971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.263

Hom.:

24024

Bravo

AF:

0.250

Asia WGS

AF:

0.230

AC:

797

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

(source)

DANN

Benign

0.55

PhyloP100

-0.46

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

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