rs7189819

Variant names:

• chr16-53502433-C-T
• rs7189819
• NM_022476.4:c.-71+714G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022476.4(AKTIP):​c.-71+714G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,134 control chromosomes in the GnomAD database, including 8,227 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 0.32 (8227 hom., cov: 33)
• Consequence: AKTIP NM_022476.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 16 publications found

Genes affected

AKTIP (HGNC:16710): (AKT interacting protein) The mouse homolog of this gene produces fused toes and thymic hyperplasia in heterozygous mutant animals while homozygous mutants die in early development. This gene may play a role in apoptosis as these morphological abnormalities are caused by altered patterns of programmed cell death. The protein encoded by this gene is similar to the ubiquitin ligase domain of other ubiquitin-conjugating enzymes but lacks the conserved cysteine residue that enables those enzymes to conjugate ubiquitin to the target protein. This protein interacts directly with serine/threonine kinase protein kinase B (PKB)/Akt and modulates PKB activity by enhancing the phosphorylation of PKB's regulatory sites. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKTIP	NM_022476.4	c.-71+714G>A		intron_variant	Intron 1 of 9	ENST00000394657.12	NP_071921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKTIP	ENST00000394657.12	c.-71+714G>A		intron_variant	Intron 1 of 9	2	NM_022476.4	ENSP00000378152.6

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48268 AN: 152016 Hom.: 8209 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.318 AC: 48325 AN: 152134 Hom.: 8227 Cov.: 33 AF XY: 0.311 AC XY: 23145 AN XY: 74378

African (AFR) AF: 0.396 AC: 16435 AN: 41474

American (AMR) AF: 0.289 AC: 4414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3472

East Asian (EAS) AF: 0.0506 AC: 262 AN: 5176

South Asian (SAS) AF: 0.199 AC: 962 AN: 4828

European-Finnish (FIN) AF: 0.240 AC: 2542 AN: 10580

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21609 AN: 67988

Other (OTH) AF: 0.340 AC: 719 AN: 2116

Alfa AF: 0.319 Hom.: 13266

Bravo AF: 0.323

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.80
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7189819; hg19: chr16-53536345;