chr15-85531675-C-T

Variant names:

• chr15-85531675-C-T
• rs2344436
• NM_007200.5:c.182-1909C>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.182-1909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,004 control chromosomes in the GnomAD database, including 21,119 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 0.52 (21119 hom., cov: 32)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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.182-1909C>T		intron	N/A	NP_009131.2
	AKAP13	NM_006738.6		c.182-1909C>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.182-1909C>T		intron	N/A	ENSP00000378026.3
	AKAP13	ENST00000361243.6	TSL:1	c.182-1909C>T		intron	N/A	ENSP00000354718.2
	AKAP13	ENST00000560302.5	TSL:1	c.182-1909C>T		intron	N/A	ENSP00000453634.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79238 AN: 151886 Hom.: 21114 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.522 AC: 79286 AN: 152004 Hom.: 21119 Cov.: 32 AF XY: 0.515 AC XY: 38253 AN XY: 74274

African (AFR) AF: 0.551 AC: 22842 AN: 41430

American (AMR) AF: 0.506 AC: 7720 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2116 AN: 3466

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5176

South Asian (SAS) AF: 0.291 AC: 1403 AN: 4818

European-Finnish (FIN) AF: 0.500 AC: 5270 AN: 10542

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36975 AN: 67988

Other (OTH) AF: 0.548 AC: 1159 AN: 2114

Alfa AF: 0.526 Hom.: 12596

Bravo AF: 0.530

Asia WGS AF: 0.281 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		-0.38
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: rs2344436; hg19: chr15-86074906;