rs6967

Positions:

• chr17-57121059-C-T

Variant summary

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

The NM_003488.4(AKAP1):​c.*735C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,486 control chromosomes in the GnomAD database, including 2,295 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 0.17 (2288 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7 hom.)
• Consequence: AKAP1 NM_003488.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

AKAP1 (HGNC:367): (A-kinase anchoring protein 1) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein binds to type I and type II regulatory subunits of PKA and anchors them to the mitochondrion. This protein is speculated to be involved in the cAMP-dependent signal transduction pathway and in directing RNA to a specific cellular compartment. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP1	NM_003488.4	c.*735C>T		3_prime_UTR_variant	11/11	ENST00000337714.8	NP_003479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP1	ENST00000337714.8	c.*735C>T		3_prime_UTR_variant	11/11	1	NM_003488.4	ENSP00000337736	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25356 AN: 152030 Hom.: 2281 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.160 AC: 54 AN: 338 Hom.: 7 Cov.: 0 AF XY: 0.181 AC XY: 37 AN XY: 204

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.167 AC: 25402 AN: 152148 Hom.: 2288 Cov.: 32 AF XY: 0.165 AC XY: 12306 AN XY: 74380

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.157

Alfa AF: 0.148 Hom.: 2419

Bravo AF: 0.166

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.77

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: rs6967; hg19: chr17-55198420;