rs4938013

chr11-113393748-A-Cchr11-113393748-A-Gchr11-113393748-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178510.2(ANKK1):c.453A>C(p.Ile151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,609,924 control chromosomes in the GnomAD database, including 361,510 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 0.69 (36202 hom., cov: 32)
  • Exomes 𝑓: 0.67 (325308 hom.)
• Consequence: ANKK1 NM_178510.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

ANKK1 (HGNC:21027): (ankyrin repeat and kinase domain containing 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways. This gene is closely linked to DRD2 gene (GeneID:1813) on chr 11, and a well studied restriction fragment length polymorphism (RFLP) designated TaqIA, was originally associated with the DRD2 gene, however, later was determined to be located in exon 8 of ANKK1 gene (PMIDs: 18621654, 15146457), where it causes a nonconservative amino acid substitution. It is not clear if this gene plays any role in neuropsychiatric disorders previously associated with Taq1A RFLP. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKK1	NM_178510.2	c.453A>C	p.Ile151=	synonymous_variant	2/8	ENST00000303941.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKK1	ENST00000303941.4	c.453A>C	p.Ile151=	synonymous_variant	2/8	1	NM_178510.2	P1
ANKK1	ENST00000542948.1	c.117A>C	p.Ile39=	synonymous_variant, NMD_transcript_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104276 AN: 151900 Hom.: 36182 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.687

GnomAD3 exomes AF: 0.638 AC: 156935 AN: 245936 Hom.: 50944 AF XY: 0.641 AC XY: 85635 AN XY: 133516

Gnomad AFR exome AF: 0.783

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.565

Gnomad SAS exome AF: 0.608

Gnomad FIN exome AF: 0.681

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.666 AC: 971528 AN: 1457904 Hom.: 325308 Cov.: 70 AF XY: 0.665 AC XY: 482085 AN XY: 725042

Gnomad4 AFR exome AF: 0.777

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.616

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.686 AC: 104344 AN: 152020 Hom.: 36202 Cov.: 32 AF XY: 0.682 AC XY: 50694 AN XY: 74302

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.683

Alfa AF: 0.674 Hom.: 59055

Bravo AF: 0.683

Asia WGS AF: 0.563 AC: 1956 AN: 3478

EpiCase AF: 0.674

EpiControl AF: 0.678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	1.8
Dann	Benign	0.67

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: rs4938013; hg19: chr11-113264470; COSMIC: COSV58273012;