NM_015447.4:c.4527C>G

Variant names:

• chr9-135811591-G-C
• rs147212718
• NM_015447.4:c.4527C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_015447.4(CAMSAP1):​c.4527C>G​(p.Ala1509Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.00686 in 1,592,592 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (51 hom.)
• Consequence: CAMSAP1 NM_015447.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.56
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 9-135811591-G-C is Benign according to our data. Variant chr9-135811591-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3777773.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015447.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP1	NM_015447.4	MANE Select	c.4527C>G	p.Ala1509Ala	synonymous	Exon 17 of 17	NP_056262.3	Q5T5Y3-1
	CAMSAP1	NM_001437279.1		c.4560C>G	p.Ala1520Ala	synonymous	Exon 18 of 18	NP_001424208.1
	CAMSAP1	NM_001437280.1		c.4095C>G	p.Ala1365Ala	synonymous	Exon 16 of 16	NP_001424209.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP1	ENST00000389532.9	TSL:5 MANE Select	c.4527C>G	p.Ala1509Ala	synonymous	Exon 17 of 17	ENSP00000374183.4	Q5T5Y3-1
	CAMSAP1	ENST00000312405.10	TSL:1	c.3693C>G	p.Ala1231Ala	synonymous	Exon 15 of 15	ENSP00000312463.6	Q5T5Y3-2
	CAMSAP1	ENST00000409386.3	TSL:5	c.4560C>G	p.Ala1520Ala	synonymous	Exon 18 of 18	ENSP00000386420.3	Q5T5Y3-3

Frequencies

GnomAD3 genomes AF: 0.00567 AC: 863 AN: 152192 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00864

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00625 AC: 1334 AN: 213314 AF XY: 0.00642

Gnomad AFR exome AF: 0.000831

Gnomad AMR exome AF: 0.00488

Gnomad ASJ exome AF: 0.0161

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00229

Gnomad NFE exome AF: 0.00835

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00698 AC: 10060 AN: 1440282 Hom.: 51 Cov.: 30 AF XY: 0.00715 AC XY: 5107 AN XY: 714268

African (AFR) AF: 0.000999 AC: 33 AN: 33026

American (AMR) AF: 0.00558 AC: 230 AN: 41238

Ashkenazi Jewish (ASJ) AF: 0.0168 AC: 433 AN: 25702

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38844

South Asian (SAS) AF: 0.00543 AC: 450 AN: 82926

European-Finnish (FIN) AF: 0.00236 AC: 123 AN: 52098

Middle Eastern (MID) AF: 0.00817 AC: 47 AN: 5750

European-Non Finnish (NFE) AF: 0.00752 AC: 8277 AN: 1101044

Other (OTH) AF: 0.00781 AC: 466 AN: 59654

GnomAD4 genome AF: 0.00567 AC: 863 AN: 152310 Hom.: 5 Cov.: 33 AF XY: 0.00567 AC XY: 422 AN XY: 74478

African (AFR) AF: 0.00123 AC: 51 AN: 41564

American (AMR) AF: 0.00582 AC: 89 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00600 AC: 29 AN: 4830

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00866 AC: 589 AN: 68028

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00753 Hom.: 2

Bravo AF: 0.00569

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.4
DANN	Benign	0.72
PhyloP100		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs147212718; hg19: chr9-138703437;