rs3777486

Variant names:

• chr6-131263508-T-C
• rs3777486
• NM_016377.4:c.851-18022T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

ENSG00000290067 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKAP7	NM_016377.4	c.851-18022T>C		intron_variant	Intron 7 of 7	ENST00000431975.7	NP_057461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP7	ENST00000431975.7	c.851-18022T>C		intron_variant	Intron 7 of 7	2	NM_016377.4	ENSP00000405252.2

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

African (AFR) AF: 0.0697 AC: 2896 AN: 41556

American (AMR) AF: 0.195 AC: 2974 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3470

East Asian (EAS) AF: 0.0966 AC: 501 AN: 5188

South Asian (SAS) AF: 0.121 AC: 582 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1569 AN: 10608

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8534 AN: 68014

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.111 Hom.: 302

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
PhyloP100		0.086
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: rs3777486; hg19: chr6-131584648;