chr14-32573797-G-A

Variant names:

• chr14-32573797-G-A
• rs1956211
• NM_004274.5:c.2347-3323G>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.2347-3323G>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
• 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=-0.8).
• 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 rank	MANE	Protein	UniProt
AKAP6	NM_004274.5	c.2347-3323G>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.2347-3323G>A		intron_variant	Intron 4 of 13	1	NM_004274.5	ENSP00000280979.4
AKAP6	ENST00000557354.5	c.2347-3323G>A		intron_variant	Intron 4 of 9	1		ENSP00000450531.1
AKAP6	ENST00000557272.1	c.2347-3323G>A		intron_variant	Intron 4 of 12	5		ENSP00000451247.1

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

African (AFR) AF: 0.801 AC: 33221 AN: 41500

American (AMR) AF: 0.839 AC: 12815 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3028 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4668 AN: 5142

South Asian (SAS) AF: 0.808 AC: 3889 AN: 4814

European-Finnish (FIN) AF: 0.759 AC: 8026 AN: 10570

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52480 AN: 67986

Other (OTH) AF: 0.828 AC: 1749 AN: 2112

Alfa AF: 0.781 Hom.: 178652

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
PhyloP100		-0.69
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: rs1956211; hg19: chr14-33043003;