rs11638762

Variant names:

• chr15-85617210-A-T
• rs11638762
• NM_007200.5:c.4162-22164A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.96).
• 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 rank	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.4162-22164A>T		intron_variant	Intron 8 of 36	ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.4162-22164A>T		intron_variant	Intron 8 of 36		NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.4162-22164A>T		intron_variant	Intron 8 of 36	1	NM_007200.5	ENSP00000378026.3
AKAP13	ENST00000361243.6	c.4162-22164A>T		intron_variant	Intron 8 of 36	1		ENSP00000354718.2
AKAP13	ENST00000559362.5	c.4162-22164A>T		intron_variant	Intron 8 of 14	2		ENSP00000453768.1
AKAP13	ENST00000560340.5	c.121-22164A>T		intron_variant	Intron 2 of 3	4		ENSP00000483091.1

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

African (AFR) AF: 0.501 AC: 20746 AN: 41448

American (AMR) AF: 0.503 AC: 7692 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1855 AN: 3468

East Asian (EAS) AF: 0.593 AC: 3065 AN: 5172

South Asian (SAS) AF: 0.440 AC: 2124 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3359 AN: 10560

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28815 AN: 67936

Other (OTH) AF: 0.475 AC: 1003 AN: 2112

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
PhyloP100		-0.60
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: rs11638762; hg19: chr15-86160441;