14-32571979-A-T

Variant names:

• chr14-32571979-A-T
• rs719851
• NM_004274.5:c.2347-5141A>T

Variant summary

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

The NM_004274.5(AKAP6):​c.2347-5141A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,174 control chromosomes in the GnomAD database, including 4,682 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 0.24 (4682 hom., cov: 33)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 2 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 = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.2347-5141A>T		intron_variant	Intron 4 of 13	ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.2347-5141A>T		intron_variant	Intron 4 of 13	1	NM_004274.5	ENSP00000280979.4
AKAP6	ENST00000557354.5	c.2347-5141A>T		intron_variant	Intron 4 of 9	1		ENSP00000450531.1
AKAP6	ENST00000557272.1	c.2347-5141A>T		intron_variant	Intron 4 of 12	5		ENSP00000451247.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36048 AN: 152056 Hom.: 4688 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.237 AC: 36037 AN: 152174 Hom.: 4682 Cov.: 33 AF XY: 0.244 AC XY: 18166 AN XY: 74372

African (AFR) AF: 0.174 AC: 7225 AN: 41524

American (AMR) AF: 0.200 AC: 3061 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3470

East Asian (EAS) AF: 0.580 AC: 3005 AN: 5178

South Asian (SAS) AF: 0.273 AC: 1319 AN: 4826

European-Finnish (FIN) AF: 0.302 AC: 3189 AN: 10574

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16203 AN: 67988

Other (OTH) AF: 0.261 AC: 551 AN: 2114

Alfa AF: 0.239 Hom.: 565

Bravo AF: 0.229

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.70
PhyloP100		0.58
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: rs719851; hg19: chr14-33041185;