Genetic Variant CAMSAP1:c.1223+1132T>C (chr9-135826275-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015447.4(CAMSAP1):c.1223+1132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,262 control chromosomes in the GnomAD database, including 60,067 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 0.89 ( 59993 hom., cov: 30)

Exomes 𝑓: 0.91 ( 74 hom. )

Consequence

CAMSAP1
NM_015447.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.634

Publications

4 publications found

Variant links:

Genes affected

CAMSAP1 (HGNC:19946): (calmodulin regulated spectrin associated protein 1) Enables microtubule minus-end binding activity and spectrin binding activity. Involved in several processes, including neuron projection development; regulation of cell morphogenesis; and regulation of microtubule polymerization. Located in microtubule. Colocalizes with microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

CAMSAP1 Gene-Disease associations (from GenCC):

cortical dysplasia, complex, with other brain malformations 12
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

CAMSAP1 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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP1	NM_015447.4 link	c.1223+1132T>C		intron_variant	Intron 8 of 16	ENST00000389532.9	NP_056262.3	Q5T5Y3-1A0A384NY94

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CAMSAP1	ENST00000389532.9 link	c.1223+1132T>C	intron_variant	Intron 8 of 16	5	NM_015447.4	ENSP00000374183.4	Q5T5Y3-1
CAMSAP1	ENST00000312405.10 link	c.389+1132T>C	intron_variant	Intron 6 of 14	1		ENSP00000312463.6	Q5T5Y3-2
CAMSAP1	ENST00000483991.5 link	n.135T>C	non_coding_transcript_exon_variant	Exon 1 of 11	2
CAMSAP1	ENST00000409386.3 link	c.1256+1132T>C	intron_variant	Intron 9 of 17	5		ENSP00000386420.3	Q5T5Y3-3

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

134917

AN:

151968

Hom.:

59942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.847

Gnomad EAS

AF:

0.980

Gnomad SAS

AF:

0.948

Gnomad FIN

AF:

0.827

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.873

GnomAD4 exome

AF:

0.909

AC:

160

AN:

176

Hom.:

Cov.:

AF XY:

0.910

AC XY:

111

AN XY:

122

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.899

AC:

124

AN:

138

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.888

AC:

135024

AN:

152086

Hom.:

59993

Cov.:

AF XY:

0.888

AC XY:

66016

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.923

AC:

38316

AN:

41492

American (AMR)

AF:

0.900

AC:

13766

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.847

AC:

2938

AN:

3468

East Asian (EAS)

AF:

0.980

AC:

5055

AN:

5160

South Asian (SAS)

AF:

0.946

AC:

4554

AN:

4812

European-Finnish (FIN)

AF:

0.827

AC:

8752

AN:

10578

Middle Eastern (MID)

AF:

0.878

AC:

258

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58870

AN:

67964

Other (OTH)

AF:

0.875

AC:

1847

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

771

1543

2314

3086

3857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.877

Hom.:

113190

Bravo

AF:

0.892

Asia WGS

AF:

0.964

AC:

3353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.42

(source)

DANN

Benign

0.20

PhyloP100

-0.63

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