rs3777486

Positions:

• chr6-131263508-T-C

Variant summary

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

The NM_016377.4(AKAP7):​c.851-18022T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,262 control chromosomes in the GnomAD database, including 1,200 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 (1200 hom., cov: 32)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP7	NM_016377.4	c.851-18022T>C		intron_variant		ENST00000431975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP7	ENST00000431975.7	c.851-18022T>C		intron_variant		2	NM_016377.4	P1
	ENST00000702750.1	n.339-45600A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17805 AN: 152144 Hom.: 1200 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.117 AC: 17806 AN: 152262 Hom.: 1200 Cov.: 32 AF XY: 0.119 AC XY: 8861 AN XY: 74444

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0966

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.110

Alfa AF: 0.118 Hom.: 283

Bravo AF: 0.119

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.50

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: rs3777486; hg19: chr6-131584648;