rs6459541

Positions:

• chr6-17405815-G-A
• chr6-17405815-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006366.3(CAP2):​c.-2+12069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,936 control chromosomes in the GnomAD database, including 11,416 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 0.36 (11416 hom., cov: 32)
• Consequence: CAP2 NM_006366.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

Genes affected

CAP2 (HGNC:20039): (cyclase associated actin cytoskeleton regulatory protein 2) This gene was identified by its similarity to the gene for human adenylyl cyclase-associated protein. The function of the protein encoded by this gene is unknown. However, the protein appears to be able to interact with adenylyl cyclase-associated protein and actin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAP2	NM_006366.3	c.-2+12069G>A		intron_variant		ENST00000229922.7
CAP2	NM_001363533.2	c.-2+12069G>A		intron_variant
CAP2	NM_001363534.2	c.-2+12069G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAP2	ENST00000229922.7	c.-2+12069G>A		intron_variant		1	NM_006366.3	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55185 AN: 151818 Hom.: 11383 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.364 AC: 55259 AN: 151936 Hom.: 11416 Cov.: 32 AF XY: 0.360 AC XY: 26762 AN XY: 74248

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.343

Alfa AF: 0.323 Hom.: 1115

Bravo AF: 0.368

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs6459541; hg19: chr6-17406046;