6-131205365-A-G

Variant names:

• chr6-131205365-A-G
• rs3777474
• NM_016377.4:c.702+5792A>G

Variant summary

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

The NM_016377.4(AKAP7):​c.702+5792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,576 control chromosomes in the GnomAD database, including 10,874 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 0.38 (10874 hom., cov: 29)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP7	NM_016377.4	c.702+5792A>G		intron_variant	Intron 6 of 7	ENST00000431975.7	NP_057461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP7	ENST00000431975.7	c.702+5792A>G		intron_variant	Intron 6 of 7	2	NM_016377.4	ENSP00000405252.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56793 AN: 151456 Hom.: 10856 Cov.: 29

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.375 AC: 56856 AN: 151576 Hom.: 10874 Cov.: 29 AF XY: 0.371 AC XY: 27512 AN XY: 74064

African (AFR) AF: 0.430 AC: 17742 AN: 41276

American (AMR) AF: 0.346 AC: 5264 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1339 AN: 3462

East Asian (EAS) AF: 0.217 AC: 1118 AN: 5150

South Asian (SAS) AF: 0.250 AC: 1201 AN: 4798

European-Finnish (FIN) AF: 0.363 AC: 3797 AN: 10474

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25043 AN: 67882

Other (OTH) AF: 0.369 AC: 776 AN: 2102

Alfa AF: 0.377 Hom.: 1365

Bravo AF: 0.377

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		-0.083
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: rs3777474; hg19: chr6-131526505;