rs4938013

Variant names:

• chr11-113393748-A-C
• rs4938013
• NM_178510.2:c.453A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-113393748-A-C
• chr11-113393748-A-G
• chr11-113393748-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178510.2(ANKK1):​c.453A>C​(p.Ile151Ile) 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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANKK1	NM_178510.2	c.453A>C	p.Ile151Ile	synonymous_variant	Exon 2 of 8	ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4	c.453A>C	p.Ile151Ile	synonymous_variant	Exon 2 of 8	1	NM_178510.2	ENSP00000306678.3
ANKK1	ENST00000542948.1	n.114A>C		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000445810.1

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

GnomAD2 exomes AF: 0.638 AC: 156935 AN: 245936 AF XY: 0.641

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 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

African (AFR) AF: 0.777 AC: 25989 AN: 33468

American (AMR) AF: 0.506 AC: 22605 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 17921 AN: 26096

East Asian (EAS) AF: 0.583 AC: 23115 AN: 39670

South Asian (SAS) AF: 0.616 AC: 53070 AN: 86176

European-Finnish (FIN) AF: 0.683 AC: 34626 AN: 50714

Middle Eastern (MID) AF: 0.651 AC: 3746 AN: 5758

European-Non Finnish (NFE) AF: 0.675 AC: 749825 AN: 1111048

Other (OTH) AF: 0.674 AC: 40631 AN: 60318

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

African (AFR) AF: 0.778 AC: 32288 AN: 41478

American (AMR) AF: 0.585 AC: 8934 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2336 AN: 3472

East Asian (EAS) AF: 0.566 AC: 2921 AN: 5164

South Asian (SAS) AF: 0.597 AC: 2870 AN: 4810

European-Finnish (FIN) AF: 0.669 AC: 7065 AN: 10568

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.671 AC: 45582 AN: 67956

Other (OTH) AF: 0.683 AC: 1439 AN: 2106

Alfa AF: 0.676 Hom.: 134843

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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