rs2016844

Positions:

• chr11-8917387-C-T

Variant summary

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

The NM_020642.4(AKIP1):​c.489+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,600,172 control chromosomes in the GnomAD database, including 94,047 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 0.28 (6937 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87110 hom.)
• Consequence: AKIP1 NM_020642.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

Genes affected

AKIP1 (HGNC:1170): (A-kinase interacting protein 1) This gene encodes a nuclear protein that interacts with protein kinase A catalytic subunit, and regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.97712E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIP1	NM_020642.4	c.489+20C>T		intron_variant		ENST00000309377.9	NP_065693.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKIP1	ENST00000309377.9	c.489+20C>T		intron_variant		1	NM_020642.4	ENSP00000310459	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42799 AN: 151978 Hom.: 6932 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.323 AC: 79976 AN: 247298 Hom.: 14095 AF XY: 0.337 AC XY: 45111 AN XY: 133828

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.442

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.325

GnomAD4 exome AF: 0.341 AC: 494067 AN: 1448074 Hom.: 87110 Cov.: 28 AF XY: 0.346 AC XY: 249597 AN XY: 721042

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.448

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.439

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.281 AC: 42813 AN: 152098 Hom.: 6937 Cov.: 32 AF XY: 0.282 AC XY: 20924 AN XY: 74328

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.312

Alfa AF: 0.333 Hom.: 2084

Bravo AF: 0.267

TwinsUK AF: 0.344 AC: 1276

ALSPAC AF: 0.359 AC: 1384

ESP6500AA AF: 0.133 AC: 586

ESP6500EA AF: 0.355 AC: 3046

ExAC AF: 0.324 AC: 39280

Asia WGS AF: 0.324 AC: 1130 AN: 3478

EpiCase AF: 0.377

EpiControl AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.22
DANN	Benign	0.64
DEOGEN2	Benign	0.014	.;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.35	.;T;T;T
MetaRNN	Benign	0.00040	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PROVEAN	Benign	-0.70	N;N;N;N
REVEL	Benign	0.0050
Sift	Benign	0.24	T;T;T;T
Sift4G	Pathogenic	0.0	D;D;.;D
Polyphen		0.010	B;B;.;B
Vest4		0.17
ClinPred		0.0024	T
GERP RS		-5.7

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: rs2016844; hg19: chr11-8938934;