Genetic Variant NM_007056.3:c.99+218C>T (chr19-45040529-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_007056.3(CLASRP):c.99+218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 423,822 control chromosomes in the GnomAD database, including 52,643 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 0.47 ( 17555 hom., cov: 32)

Exomes 𝑓: 0.50 ( 35088 hom. )

Consequence

CLASRP
NM_007056.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

20 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

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.99+218C>T	intron	N/A	NP_008987.2	Q8N2M8-1
CLASRP	NM_001278439.2		c.99+218C>T	intron	N/A	NP_001265368.1	Q8N2M8-4
CLASRP	NR_103529.2		n.192+218C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLASRP	ENST00000221455.8	TSL:1 MANE Select	c.99+218C>T	intron	N/A	ENSP00000221455.3	Q8N2M8-1
CLASRP	ENST00000391952.7	TSL:1	n.99+218C>T	intron	N/A	ENSP00000375814.2	Q8N2M8-3
CLASRP	ENST00000587112.1	TSL:1	n.42+218C>T	intron	N/A	ENSP00000466371.1	K7EM61

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

71930

AN:

151782

Hom.:

17553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.548

Gnomad OTH

AF:

0.496

GnomAD4 exome

AF:

0.501

AC:

136249

AN:

271922

Hom.:

35088

Cov.:

AF XY:

0.494

AC XY:

71604

AN XY:

144808

show subpopulations

African (AFR)

AF:

0.366

AC:

2975

AN:

8122

American (AMR)

AF:

0.450

AC:

6051

AN:

13434

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

3860

AN:

8020

East Asian (EAS)

AF:

0.438

AC:

7698

AN:

17582

South Asian (SAS)

AF:

0.386

AC:

13937

AN:

36086

European-Finnish (FIN)

AF:

0.498

AC:

7586

AN:

15232

Middle Eastern (MID)

AF:

0.544

AC:

607

AN:

1116

European-Non Finnish (NFE)

AF:

0.546

AC:

86008

AN:

157390

Other (OTH)

AF:

0.504

AC:

7527

AN:

14940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3179

6358

9536

12715

15894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.474

AC:

71950

AN:

151900

Hom.:

17555

Cov.:

AF XY:

0.469

AC XY:

34839

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.363

AC:

15032

AN:

41408

American (AMR)

AF:

0.460

AC:

7006

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1673

AN:

3470

East Asian (EAS)

AF:

0.424

AC:

2188

AN:

5162

South Asian (SAS)

AF:

0.395

AC:

1898

AN:

4802

European-Finnish (FIN)

AF:

0.494

AC:

5214

AN:

10552

Middle Eastern (MID)

AF:

0.541

AC:

158

AN:

292

European-Non Finnish (NFE)

AF:

0.548

AC:

37264

AN:

67984

Other (OTH)

AF:

0.498

AC:

1048

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1917

3834

5750

7667

9584

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<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:

0.523

Hom.:

35794

Bravo

AF:

0.467

Asia WGS

AF:

0.428

AC:

1491

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

(source)

DANN

Benign

0.75

PhyloP100

0.099

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over