rs1956211

chr14-32573797-G-Achr14-32573797-G-Cchr14-32573797-G-T

Variant summary

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

The NM_004274.5(AKAP6):c.2347-3323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,074 control chromosomes in the GnomAD database, including 48,121 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 0.79 (48121 hom., cov: 32)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP6	NM_004274.5	c.2347-3323G>A		intron_variant		ENST00000280979.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP6	ENST00000280979.9	c.2347-3323G>A		intron_variant		1	NM_004274.5	P1
AKAP6	ENST00000557354.5	c.2347-3323G>A		intron_variant		1
AKAP6	ENST00000557272.1	c.2347-3323G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120748 AN: 151956 Hom.: 48072 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.795 AC: 120856 AN: 152074 Hom.: 48121 Cov.: 32 AF XY: 0.796 AC XY: 59173 AN XY: 74330

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.828

Alfa AF: 0.780 Hom.: 76116

Bravo AF: 0.803

Asia WGS AF: 0.858 AC: 2979 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.0
Dann	Benign	0.80

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: rs1956211; hg19: chr14-33043003;