Genetic Variant CLASRP:c.864-3T>C (chr19-45062151-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007056.3(CLASRP):c.864-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,521,030 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

CLASRP
NM_007056.3 splice_region, intron

Scores

Splicing: ADA: 0.00005990

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.908

Publications

0 publications found

Variant links:

Genes affected

CLASRP (HGNC:17731): (CLK4 associating serine/arginine rich protein) Predicted to be involved in RNA splicing and mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CLASRP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 19-45062151-T-C is Benign according to our data. Variant chr19-45062151-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2650093.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007056.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASRP	NM_007056.3	MANE Select	c.864-3T>C	splice_region intron	N/A	NP_008987.2	Q8N2M8-1
CLASRP	NM_001278439.2		c.678-3T>C	splice_region intron	N/A	NP_001265368.1	Q8N2M8-4
CLASRP	NR_103529.2		n.957-3T>C	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASRP	ENST00000221455.8	TSL:1 MANE Select	c.864-3T>C	splice_region intron	N/A	ENSP00000221455.3	Q8N2M8-1
CLASRP	ENST00000391952.7	TSL:1	n.864-3T>C	splice_region intron	N/A	ENSP00000375814.2	Q8N2M8-3
CLASRP	ENST00000587112.1	TSL:1	n.*224-3T>C	splice_region intron	N/A	ENSP00000466371.1	K7EM61

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00131

AC:

328

AN:

250790

AF XY:

0.00134

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00140

AC:

1911

AN:

1368932

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

942

AN XY:

686608

show subpopulations

African (AFR)

AF:

0.000475

AC:

AN:

31592

American (AMR)

AF:

0.00319

AC:

142

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.000235

AC:

AN:

25530

East Asian (EAS)

AF:

0.00

AC:

AN:

39280

South Asian (SAS)

AF:

0.00

AC:

AN:

84380

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5598

European-Non Finnish (NFE)

AF:

0.00161

AC:

1652

AN:

1027492

Other (OTH)

AF:

0.00142

AC:

AN:

57172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

161

242

322

403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.00162

AC:

246

AN:

152098

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000651

AC:

AN:

41494

American (AMR)

AF:

0.00629

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00162

AC:

110

AN:

67970

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00145

Hom.:

Bravo

AF:

0.00209

EpiCase

AF:

0.00147

EpiControl

AF:

0.00160

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.6

(source)

DANN

Benign

0.55

PhyloP100

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over