rs3903759

chr6-131199854-C-A

Variant summary

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

The NM_016377.4(AKAP7):c.702+281C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 377,446 control chromosomes in the GnomAD database, including 3,636 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 0.12 (1318 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2318 hom.)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP7	NM_016377.4	c.702+281C>A		intron_variant		ENST00000431975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP7	ENST00000431975.7	c.702+281C>A		intron_variant		2	NM_016377.4	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18239 AN: 152068 Hom.: 1318 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.135 AC: 30461 AN: 225260 Hom.: 2318 AF XY: 0.135 AC XY: 16260 AN XY: 120306

Gnomad4 AFR exome AF: 0.0630

Gnomad4 AMR exome AF: 0.0670

Gnomad4 ASJ exome AF: 0.0750

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.120 AC: 18239 AN: 152186 Hom.: 1318 Cov.: 32 AF XY: 0.121 AC XY: 8989 AN XY: 74404

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.0759

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.0406

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.112

Alfa AF: 0.136 Hom.: 2075

Bravo AF: 0.105

Asia WGS AF: 0.0780 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.2
Dann	Benign	0.71

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: rs3903759; hg19: chr6-131520994;