6-131242437-G-A

Variant names:

• chr6-131242437-G-A
• rs4629710
• NM_016377.4:c.850+22629G>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.850+22629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,596 control chromosomes in the GnomAD database, including 1,850 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 0.14 (1850 hom., cov: 31)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP7	NM_016377.4	c.850+22629G>A		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.850+22629G>A		intron_variant	Intron 7 of 7	2	NM_016377.4	ENSP00000405252.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21169 AN: 151492 Hom.: 1850 Cov.: 31

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.140 AC: 21164 AN: 151596 Hom.: 1850 Cov.: 31 AF XY: 0.135 AC XY: 10033 AN XY: 74080

African (AFR) AF: 0.0496 AC: 2052 AN: 41390

American (AMR) AF: 0.156 AC: 2380 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5174

South Asian (SAS) AF: 0.133 AC: 637 AN: 4800

European-Finnish (FIN) AF: 0.107 AC: 1109 AN: 10386

Middle Eastern (MID) AF: 0.276 AC: 79 AN: 286

European-Non Finnish (NFE) AF: 0.196 AC: 13335 AN: 67868

Other (OTH) AF: 0.165 AC: 348 AN: 2106

Alfa AF: 0.182 Hom.: 8167

Bravo AF: 0.140

Asia WGS AF: 0.0750 AC: 262 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.22
PhyloP100		0.72
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: rs4629710; hg19: chr6-131563577;