11-113388932-A-G

Variant names:

• chr11-113388932-A-G
• rs4938012
• NM_178510.2:c.185+863A>G

Variant summary

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

The NM_178510.2(ANKK1):​c.185+863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,788 control chromosomes in the GnomAD database, including 36,068 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 (36068 hom., cov: 31)
• Consequence: ANKK1 NM_178510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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.185+863A>G		intron_variant	Intron 1 of 7	ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4	c.185+863A>G		intron_variant	Intron 1 of 7	1	NM_178510.2	ENSP00000306678.3

Frequencies

GnomAD3 genomes AF: 0.686 AC: 103979 AN: 151670 Hom.: 36048 Cov.: 31

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.685 AC: 104046 AN: 151788 Hom.: 36068 Cov.: 31 AF XY: 0.681 AC XY: 50501 AN XY: 74134

African (AFR) AF: 0.778 AC: 32242 AN: 41434

American (AMR) AF: 0.585 AC: 8934 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2332 AN: 3466

East Asian (EAS) AF: 0.564 AC: 2905 AN: 5148

South Asian (SAS) AF: 0.595 AC: 2854 AN: 4796

European-Finnish (FIN) AF: 0.667 AC: 7023 AN: 10522

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45413 AN: 67840

Other (OTH) AF: 0.683 AC: 1438 AN: 2106

Alfa AF: 0.683 Hom.: 4450

Bravo AF: 0.683

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.70
PhyloP100		-0.65
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: rs4938012; hg19: chr11-113259654;