rs17414154

Variant names:

• chr14-32567451-G-A
• rs17414154
• NM_004274.5:c.2347-9669G>A

Variant summary

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

The NM_004274.5(AKAP6):​c.2347-9669G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,110 control chromosomes in the GnomAD database, including 264 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 0.053 (264 hom., cov: 32)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004274.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP6	NM_004274.5	MANE Select	c.2347-9669G>A		intron	N/A	NP_004265.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKAP6	ENST00000280979.9	TSL:1 MANE Select	c.2347-9669G>A		intron	N/A	ENSP00000280979.4	Q13023-1
	AKAP6	ENST00000557354.5	TSL:1	c.2347-9669G>A		intron	N/A	ENSP00000450531.1	Q13023-2
	AKAP6	ENST00000851220.1		c.2347-9669G>A		intron	N/A	ENSP00000521279.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8119 AN: 151992 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0344

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0534 AC: 8130 AN: 152110 Hom.: 264 Cov.: 32 AF XY: 0.0535 AC XY: 3979 AN XY: 74348

African (AFR) AF: 0.0568 AC: 2357 AN: 41486

American (AMR) AF: 0.0343 AC: 525 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.0481 AC: 232 AN: 4820

European-Finnish (FIN) AF: 0.0727 AC: 768 AN: 10558

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0571 AC: 3881 AN: 68002

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0557 Hom.: 35

Bravo AF: 0.0505

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.68
PhyloP100		-1.1
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: rs17414154; hg19: chr14-33036657;