Genetic Variant CAPRIN1:c.217-4A>G (chr11-34071722-A-G) – 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_005898.5(CAPRIN1):c.217-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,605,760 control chromosomes in the GnomAD database, including 33 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 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 32 hom. )

Consequence

CAPRIN1
NM_005898.5 splice_region, intron

Scores

Splicing: ADA: 0.00005737

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.287

Variant links:

Genes affected

CAPRIN1 (HGNC:6743): (cell cycle associated protein 1) Enables RNA binding activity. Predicted to be involved in negative regulation of translation and positive regulation of dendritic spine morphogenesis. Located in cell leading edge and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CAPRIN1 links:

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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=-0.8).

BP6

Variant 11-34071722-A-G is Benign according to our data. Variant chr11-34071722-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3387887.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPRIN1	NM_005898.5 link	c.217-4A>G		splice_region_variant, intron_variant	Intron 2 of 18	ENST00000341394.9	NP_005889.3	Q14444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9 link	c.217-4A>G		splice_region_variant, intron_variant	Intron 2 of 18	1	NM_005898.5	ENSP00000340329.4		Q14444-1

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

556

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00972

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00454

AC:

1139

AN:

250928

AF XY:

0.00489

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.00259

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00721

Gnomad NFE exome

AF:

0.00471

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00406

AC:

5906

AN:

1453448

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3070

AN XY:

723764

show subpopulations

Gnomad4 AFR exome

AF:

0.000421

AC:

AN:

33264

Gnomad4 AMR exome

AF:

0.00260

AC:

116

AN:

44550

Gnomad4 ASJ exome

AF:

0.00426

AC:

111

AN:

26058

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39558

Gnomad4 SAS exome

AF:

0.00882

AC:

758

AN:

85936

Gnomad4 FIN exome

AF:

0.00691

AC:

369

AN:

53398

Gnomad4 NFE exome

AF:

0.00376

AC:

4158

AN:

1104856

Gnomad4 Remaining exome

AF:

0.00541

AC:

325

AN:

60076

Heterozygous variant carriers

272

544

816

1088

1360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

0.00365

AC:

556

AN:

152312

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000385

AC:

0.000384782

AN:

0.000384782

Gnomad4 AMR

AF:

0.00373

AC:

0.0037289

AN:

0.0037289

Gnomad4 ASJ

AF:

0.00346

AC:

0.00345622

AN:

0.00345622

Gnomad4 EAS

AF:

0.000386

AC:

0.000385505

AN:

0.000385505

Gnomad4 SAS

AF:

0.00993

AC:

0.00993377

AN:

0.00993377

Gnomad4 FIN

AF:

0.00622

AC:

0.00622172

AN:

0.00622172

Gnomad4 NFE

AF:

0.00504

AC:

0.00504204

AN:

0.00504204

Gnomad4 OTH

AF:

0.00379

AC:

0.00378788

AN:

0.00378788

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.00401

Hom.:

Bravo

AF:

0.00272

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00644

EpiControl

AF:

0.00439

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CAPRIN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.6

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over