rs7149108

Positions:

• chr14-32493094-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004274.5(AKAP6):​c.325-42460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,210 control chromosomes in the GnomAD database, including 1,859 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 0.091 (1859 hom., cov: 31)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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

Verdict is Benign. Variant got -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 = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.325-42460G>A		intron_variant		ENST00000280979.9	NP_004265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP6	ENST00000280979.9	c.325-42460G>A		intron_variant		1	NM_004274.5	ENSP00000280979	P1
AKAP6	ENST00000557354.5	c.325-42460G>A		intron_variant		1		ENSP00000450531
AKAP6	ENST00000553547.5	c.-403+18536G>A		intron_variant		2		ENSP00000451239
AKAP6	ENST00000557272.1	c.325-42460G>A		intron_variant		5		ENSP00000451247

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13890 AN: 152094 Hom.: 1851 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00833

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0915 AC: 13924 AN: 152210 Hom.: 1859 Cov.: 31 AF XY: 0.0880 AC XY: 6548 AN XY: 74422

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.0397

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00833

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0218 Hom.: 456

Bravo AF: 0.102

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.54
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs7149108; hg19: chr14-32962300;