rs1951681

chr14-32381819-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.-34-51641G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 151,984 control chromosomes in the GnomAD database, including 365 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 0.057 (365 hom., cov: 31)
• Consequence: AKAP6 NM_004274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP6	NM_004274.5	c.-34-51641G>A		intron_variant		ENST00000280979.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP6	ENST00000280979.9	c.-34-51641G>A		intron_variant		1	NM_004274.5	P1
	ENST00000557371.1	n.229+3253C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8598 AN: 151864 Hom.: 364 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0401

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0567 AC: 8621 AN: 151984 Hom.: 365 Cov.: 31 AF XY: 0.0558 AC XY: 4142 AN XY: 74296

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0292

Gnomad4 ASJ AF: 0.0116

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0437

Gnomad4 FIN AF: 0.0401

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0396 Hom.: 218

Bravo AF: 0.0560

Asia WGS AF: 0.0820 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
Dann	Benign	0.24

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: rs1951681; hg19: chr14-32851025;