NM_004274.5:c.2347-5094G>A

Variant names:

• chr14-32572026-G-A
• rs1950702
• NM_004274.5:c.2347-5094G>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.2347-5094G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,162 control chromosomes in the GnomAD database, including 4,734 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 (4734 hom., cov: 33)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 6 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=-0.93).
• 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.2347-5094G>A		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.2347-5094G>A		intron_variant	Intron 4 of 13	1	NM_004274.5	ENSP00000280979.4
AKAP6	ENST00000557354.5	c.2347-5094G>A		intron_variant	Intron 4 of 9	1		ENSP00000450531.1
AKAP6	ENST00000557272.1	c.2347-5094G>A		intron_variant	Intron 4 of 12	5		ENSP00000451247.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36364 AN: 152044 Hom.: 4739 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.239 AC: 36361 AN: 152162 Hom.: 4734 Cov.: 33 AF XY: 0.246 AC XY: 18322 AN XY: 74380

African (AFR) AF: 0.187 AC: 7769 AN: 41520

American (AMR) AF: 0.200 AC: 3060 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.580 AC: 3001 AN: 5174

South Asian (SAS) AF: 0.272 AC: 1315 AN: 4830

European-Finnish (FIN) AF: 0.300 AC: 3178 AN: 10576

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16024 AN: 67986

Other (OTH) AF: 0.257 AC: 541 AN: 2106

Alfa AF: 0.235 Hom.: 13361

Bravo AF: 0.231

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.38
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: rs1950702; hg19: chr14-33041232;