15-85428704-C-T

Variant names:

• chr15-85428704-C-T
• rs17552971
• NM_007200.5:c.-12+47906C>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.-12+47906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,224 control chromosomes in the GnomAD database, including 6,358 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 0.25 (6358 hom., cov: 32)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.-12+47906C>T		intron_variant	Intron 1 of 36	ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.-12+47906C>T		intron_variant	Intron 1 of 36		NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.-12+47906C>T		intron_variant	Intron 1 of 36	1	NM_007200.5	ENSP00000378026.3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38105 AN: 152104 Hom.: 6362 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.250 AC: 38094 AN: 152224 Hom.: 6358 Cov.: 32 AF XY: 0.246 AC XY: 18347 AN XY: 74446

African (AFR) AF: 0.0616 AC: 2558 AN: 41538

American (AMR) AF: 0.236 AC: 3606 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3472

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5190

South Asian (SAS) AF: 0.147 AC: 711 AN: 4822

European-Finnish (FIN) AF: 0.331 AC: 3510 AN: 10598

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25112 AN: 67996

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.293 Hom.: 1269

Bravo AF: 0.236

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.72
PhyloP100		0.65
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: rs17552971; hg19: chr15-85971935;