rs6496044

Variant names:

• chr15-85524075-G-A
• rs6496044
• NM_007200.5:c.181+2500G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007200.5(AKAP13):​c.181+2500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,082 control chromosomes in the GnomAD database, including 33,447 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 0.66 (33447 hom., cov: 32)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.181+2500G>A		intron_variant	Intron 3 of 36	ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.181+2500G>A		intron_variant	Intron 3 of 36		NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.181+2500G>A		intron_variant	Intron 3 of 36	1	NM_007200.5	ENSP00000378026.3
AKAP13	ENST00000361243.6	c.181+2500G>A		intron_variant	Intron 3 of 36	1		ENSP00000354718.2
AKAP13	ENST00000560302.5	c.181+2500G>A		intron_variant	Intron 3 of 3	1		ENSP00000453634.1
AKAP13	ENST00000559362.5	c.181+2500G>A		intron_variant	Intron 3 of 14	2		ENSP00000453768.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100669 AN: 151962 Hom.: 33431 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.662 AC: 100746 AN: 152082 Hom.: 33447 Cov.: 32 AF XY: 0.666 AC XY: 49489 AN XY: 74334

African (AFR) AF: 0.664 AC: 27556 AN: 41490

American (AMR) AF: 0.655 AC: 10014 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2691 AN: 5170

South Asian (SAS) AF: 0.634 AC: 3064 AN: 4832

European-Finnish (FIN) AF: 0.730 AC: 7712 AN: 10562

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44917 AN: 67962

Other (OTH) AF: 0.683 AC: 1443 AN: 2112

Alfa AF: 0.660 Hom.: 111637

Bravo AF: 0.658

Asia WGS AF: 0.588 AC: 2048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-1.2
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: rs6496044; hg19: chr15-86067306;