15-85645468-G-T

Position:

• chr15-85645468-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394518.7(AKAP13):​c.4238-350G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,092 control chromosomes in the GnomAD database, including 41,682 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 0.74 (41682 hom., cov: 31)
• Consequence: AKAP13 ENST00000394518.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

AKAP13-AS1 (HGNC:55975): (AKAP13 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.4238-350G>T		intron_variant		ENST00000394518.7	NP_009131.2
AKAP13	NM_001270546.1	c.158-350G>T		intron_variant			NP_001257475.1
AKAP13	NM_006738.6	c.4238-350G>T		intron_variant			NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.4238-350G>T		intron_variant		1	NM_007200.5	ENSP00000378026	A2
AKAP13-AS1	ENST00000558980.1	n.264+25217C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111726 AN: 151974 Hom.: 41635 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.735 AC: 111831 AN: 152092 Hom.: 41682 Cov.: 31 AF XY: 0.728 AC XY: 54092 AN XY: 74342

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.729

Alfa AF: 0.702 Hom.: 49783

Bravo AF: 0.747

Asia WGS AF: 0.621 AC: 2156 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs383872; hg19: chr15-86188699;