15-85443491-G-A

Variant names:

• chr15-85443491-G-A
• rs7176605
• NM_007200.5:c.-11-42219G>A

Variant summary

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

The NM_007200.5(AKAP13):​c.-11-42219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,014 control chromosomes in the GnomAD database, including 45,439 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 0.77 (45439 hom., cov: 31)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 0 publications found

Genes affected

AKAP13 (HGNC:371): (A-kinase anchoring protein 13) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007200.5. 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
	AKAP13	NM_007200.5	MANE Select	c.-11-42219G>A		intron	N/A	NP_009131.2
	AKAP13	NM_006738.6		c.-11-42219G>A		intron	N/A	NP_006729.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP13	ENST00000394518.7	TSL:1 MANE Select	c.-11-42219G>A		intron	N/A	ENSP00000378026.3	Q12802-1
	AKAP13	ENST00000361243.6	TSL:1	c.-11-42219G>A		intron	N/A	ENSP00000354718.2	Q12802-2
	AKAP13	ENST00000560302.5	TSL:1	c.-11-42219G>A		intron	N/A	ENSP00000453634.1	Q12802-5

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116981 AN: 151896 Hom.: 45419 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.770 AC: 117059 AN: 152014 Hom.: 45439 Cov.: 31 AF XY: 0.761 AC XY: 56549 AN XY: 74320

African (AFR) AF: 0.806 AC: 33396 AN: 41452

American (AMR) AF: 0.746 AC: 11387 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2634 AN: 3462

East Asian (EAS) AF: 0.526 AC: 2720 AN: 5172

South Asian (SAS) AF: 0.604 AC: 2912 AN: 4822

European-Finnish (FIN) AF: 0.710 AC: 7493 AN: 10556

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53921 AN: 67966

Other (OTH) AF: 0.754 AC: 1593 AN: 2112

Alfa AF: 0.779 Hom.: 5681

Bravo AF: 0.781

Asia WGS AF: 0.564 AC: 1958 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.034
DANN	Benign	0.78
PhyloP100		-2.7
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: rs7176605; hg19: chr15-85986722;