6-131145967-G-C

Position:

• chr6-131145967-G-C

Variant summary

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

The NM_016377.4(AKAP7):​c.151+551G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,068 control chromosomes in the GnomAD database, including 32,398 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 0.64 (32398 hom., cov: 32)
• Consequence: AKAP7 NM_016377.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP7	NM_016377.4	c.151+551G>C		intron_variant		ENST00000431975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP7	ENST00000431975.7	c.151+551G>C		intron_variant		2	NM_016377.4	P1
AKAP7	ENST00000541650.5	c.148+551G>C		intron_variant		5
AKAP7	ENST00000683794.1	c.151+551G>C		intron_variant
AKAP7	ENST00000366358.2	n.506+551G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97641 AN: 151952 Hom.: 32356 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.643 AC: 97730 AN: 152068 Hom.: 32398 Cov.: 32 AF XY: 0.633 AC XY: 47059 AN XY: 74340

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.634

Alfa AF: 0.644 Hom.: 3970

Bravo AF: 0.644

Asia WGS AF: 0.417 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.70

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: rs6942184; hg19: chr6-131467107;