chr15-85457875-C-T

Variant names:

• chr15-85457875-C-T
• rs1968867
• NM_007200.5:c.-11-27835C>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.-11-27835C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,976 control chromosomes in the GnomAD database, including 8,473 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 0.28 (8473 hom., cov: 31)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP13	NM_007200.5	MANE Select	c.-11-27835C>T		intron	N/A	NP_009131.2
	AKAP13	NM_006738.6		c.-11-27835C>T		intron	N/A	NP_006729.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP13	ENST00000394518.7	TSL:1 MANE Select	c.-11-27835C>T		intron	N/A	ENSP00000378026.3
	AKAP13	ENST00000361243.6	TSL:1	c.-11-27835C>T		intron	N/A	ENSP00000354718.2
	AKAP13	ENST00000560302.5	TSL:1	c.-11-27835C>T		intron	N/A	ENSP00000453634.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42739 AN: 151858 Hom.: 8455 Cov.: 31

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.282 AC: 42818 AN: 151976 Hom.: 8473 Cov.: 31 AF XY: 0.280 AC XY: 20834 AN XY: 74294

African (AFR) AF: 0.545 AC: 22576 AN: 41390

American (AMR) AF: 0.359 AC: 5485 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3468

East Asian (EAS) AF: 0.193 AC: 997 AN: 5176

South Asian (SAS) AF: 0.144 AC: 694 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10558

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10254 AN: 67996

Other (OTH) AF: 0.262 AC: 552 AN: 2106

Alfa AF: 0.226 Hom.: 727

Bravo AF: 0.317

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.45
PhyloP100		0.21
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: rs1968867; hg19: chr15-86001106;