rs4296166

Variant names:

• chr14-32483161-A-G
• rs4296166
• NM_004274.5:c.324+49344A>G

Variant summary

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

The NM_004274.5(AKAP6):​c.324+49344A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,978 control chromosomes in the GnomAD database, including 30,961 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 0.62 (30961 hom., cov: 31)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 8 publications found

Genes affected

AKAP6 (HGNC:376): (A-kinase anchoring protein 6) 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. The encoded protein is highly expressed in various brain regions and cardiac and skeletal muscle. It is specifically localized to the sarcoplasmic reticulum and nuclear membrane, and is involved in anchoring PKA to the nuclear membrane or sarcoplasmic reticulum. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.324+49344A>G		intron_variant	Intron 2 of 13	ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.324+49344A>G		intron_variant	Intron 2 of 13	1	NM_004274.5	ENSP00000280979.4
AKAP6	ENST00000557354.5	c.324+49344A>G		intron_variant	Intron 2 of 9	1		ENSP00000450531.1
AKAP6	ENST00000557272.1	c.324+49344A>G		intron_variant	Intron 2 of 12	5		ENSP00000451247.1
AKAP6	ENST00000553547.5	c.-403+8603A>G		intron_variant	Intron 1 of 2	2		ENSP00000451239.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94847 AN: 151860 Hom.: 30916 Cov.: 31

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.625 AC: 94952 AN: 151978 Hom.: 30961 Cov.: 31 AF XY: 0.630 AC XY: 46769 AN XY: 74276

African (AFR) AF: 0.782 AC: 32423 AN: 41484

American (AMR) AF: 0.664 AC: 10135 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3468

East Asian (EAS) AF: 0.860 AC: 4458 AN: 5186

South Asian (SAS) AF: 0.793 AC: 3817 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5493 AN: 10512

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34795 AN: 67936

Other (OTH) AF: 0.601 AC: 1265 AN: 2106

Alfa AF: 0.555 Hom.: 56241

Bravo AF: 0.638

Asia WGS AF: 0.819 AC: 2836 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.82
PhyloP100		0.18
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: rs4296166; hg19: chr14-32952367;