chr6-131181488-G-A

Variant names:

• chr6-131181488-G-A
• rs17060099
• NM_016377.4:c.589+12215G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016377.4(AKAP7):​c.589+12215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 152,256 control chromosomes in the GnomAD database, including 145 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 0.014 (145 hom., cov: 32)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 2 publications found

Genes affected

AKAP7 (HGNC:377): (A-kinase anchoring protein 7) This gene encodes a member of the A-kinase anchoring protein (AKAP) family, a group of functionally related proteins that bind to a regulatory subunit (RII) of cAMP-dependent protein kinase A (PKA) and target the enzyme to specific subcellular compartments. AKAPs have a common RII-binding domain, but contain different targeting motifs responsible for directing PKA to distinct intracellular locations. Three alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP7	NM_016377.4	c.589+12215G>A		intron_variant	Intron 5 of 7	ENST00000431975.7	NP_057461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP7	ENST00000431975.7	c.589+12215G>A		intron_variant	Intron 5 of 7	2	NM_016377.4	ENSP00000405252.2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2150 AN: 152138 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00425

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0142 AC: 2162 AN: 152256 Hom.: 145 Cov.: 32 AF XY: 0.0156 AC XY: 1163 AN XY: 74446

African (AFR) AF: 0.00176 AC: 73 AN: 41536

American (AMR) AF: 0.0668 AC: 1021 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.176 AC: 911 AN: 5182

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4824

European-Finnish (FIN) AF: 0.00425 AC: 45 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68034

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.0177 Hom.: 22

Bravo AF: 0.0216

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.43
PhyloP100		-1.7
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: rs17060099; hg19: chr6-131502628;