chr6-131172269-C-T

Position:

• chr6-131172269-C-T

Variant summary

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

The NM_016377.4(AKAP7):​c.589+2996C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,160 control chromosomes in the GnomAD database, including 601 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 0.080 (601 hom., cov: 32)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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]

AKAP7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP7	NM_016377.4	c.589+2996C>T		intron_variant		ENST00000431975.7	NP_057461.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP7	ENST00000431975.7	c.589+2996C>T		intron_variant		2	NM_016377.4	ENSP00000405252.2

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12243 AN: 152042 Hom.: 602 Cov.: 32

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0805 AC: 12245 AN: 152160 Hom.: 601 Cov.: 32 AF XY: 0.0771 AC XY: 5739 AN XY: 74402

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0928

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0967 Hom.: 376

Bravo AF: 0.0816

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.53

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: rs10499182; hg19: chr6-131493409; COSMIC: COSV63505002; COSMIC: COSV63505002;