rs11638762

chr15-85617210-A-T

Variant summary

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

The NM_007200.5(AKAP13):c.4162-22164A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,008 control chromosomes in the GnomAD database, including 16,108 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 0.46 (16108 hom., cov: 32)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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

Verdict is Benign. Variant got -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 = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP13	NM_007200.5	c.4162-22164A>T		intron_variant		ENST00000394518.7
AKAP13	NM_006738.6	c.4162-22164A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP13	ENST00000394518.7	c.4162-22164A>T		intron_variant		1	NM_007200.5	A2
AKAP13	ENST00000361243.6	c.4162-22164A>T		intron_variant		1		A2
AKAP13	ENST00000559362.5	c.4162-22164A>T		intron_variant		2
AKAP13	ENST00000560340.5	c.121-22164A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69239 AN: 151890 Hom.: 16099 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.456 AC: 69287 AN: 152008 Hom.: 16108 Cov.: 32 AF XY: 0.454 AC XY: 33714 AN XY: 74314

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.475

Alfa AF: 0.427 Hom.: 1751

Bravo AF: 0.471

Asia WGS AF: 0.508 AC: 1766 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	0.98
Dann	Benign	0.38

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: rs11638762; hg19: chr15-86160441;