15-85645468-G-T

Variant names:

• chr15-85645468-G-T
• rs383872
• NM_007200.5:c.4238-350G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394518.7. 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.4238-350G>T		intron	N/A	NP_009131.2
	AKAP13	NM_006738.6		c.4238-350G>T		intron	N/A	NP_006729.4
	AKAP13	NM_001270546.1		c.158-350G>T		intron	N/A	NP_001257475.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP13	ENST00000394518.7	TSL:1 MANE Select	c.4238-350G>T		intron	N/A	ENSP00000378026.3
	AKAP13	ENST00000361243.6	TSL:1	c.4238-350G>T		intron	N/A	ENSP00000354718.2
	AKAP13	ENST00000560676.5	TSL:1	c.158-350G>T		intron	N/A	ENSP00000481485.1

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

African (AFR) AF: 0.875 AC: 36321 AN: 41530

American (AMR) AF: 0.688 AC: 10520 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3244 AN: 5160

South Asian (SAS) AF: 0.560 AC: 2699 AN: 4818

European-Finnish (FIN) AF: 0.620 AC: 6543 AN: 10546

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47302 AN: 67970

Other (OTH) AF: 0.729 AC: 1538 AN: 2110

Alfa AF: 0.707 Hom.: 70425

Bravo AF: 0.747

Asia WGS AF: 0.621 AC: 2156 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.34
PhyloP100		-1.2
PromoterAI		-0.012	Neutral
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: rs383872; hg19: chr15-86188699;