chr9-135827810-G-C

Variant names:

• chr9-135827810-G-C
• rs3824354
• NM_015447.4:c.1046-226C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015447.4(CAMSAP1):​c.1046-226C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,228 control chromosomes in the GnomAD database, including 980 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 0.099 (980 hom., cov: 33)
• Consequence: CAMSAP1 NM_015447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP1	NM_015447.4	c.1046-226C>G		intron_variant	Intron 7 of 16	ENST00000389532.9	NP_056262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMSAP1	ENST00000389532.9	c.1046-226C>G		intron_variant	Intron 7 of 16	5	NM_015447.4	ENSP00000374183.4
CAMSAP1	ENST00000312405.10	c.212-226C>G		intron_variant	Intron 5 of 14	1		ENSP00000312463.6
CAMSAP1	ENST00000409386.3	c.1079-226C>G		intron_variant	Intron 8 of 17	5		ENSP00000386420.3

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15113 AN: 152110 Hom.: 981 Cov.: 33

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0791

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0923

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0994 AC: 15125 AN: 152228 Hom.: 980 Cov.: 33 AF XY: 0.103 AC XY: 7682 AN XY: 74434

African (AFR) AF: 0.0937 AC: 3890 AN: 41536

American (AMR) AF: 0.103 AC: 1570 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1824 AN: 5174

South Asian (SAS) AF: 0.163 AC: 788 AN: 4826

European-Finnish (FIN) AF: 0.0791 AC: 838 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0841 AC: 5719 AN: 68010

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0466 Hom.: 40

Bravo AF: 0.0996

Asia WGS AF: 0.228 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.083
DANN	Benign	0.76
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs3824354; hg19: chr9-138719656;