11-113391849-A-G

Variant names:

• chr11-113391849-A-G
• rs7123797
• NM_178510.2:c.186-1632A>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.186-1632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,882 control chromosomes in the GnomAD database, including 27,989 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 0.60 (27989 hom., cov: 31)
• Consequence: ANKK1 NM_178510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.762
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKK1	NM_178510.2	c.186-1632A>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.186-1632A>G		intron_variant	Intron 1 of 7	1	NM_178510.2	ENSP00000306678.3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91079 AN: 151764 Hom.: 27987 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.600 AC: 91116 AN: 151882 Hom.: 27989 Cov.: 31 AF XY: 0.599 AC XY: 44434 AN XY: 74216

African (AFR) AF: 0.483 AC: 19972 AN: 41374

American (AMR) AF: 0.552 AC: 8428 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2330 AN: 3464

East Asian (EAS) AF: 0.564 AC: 2899 AN: 5144

South Asian (SAS) AF: 0.568 AC: 2729 AN: 4806

European-Finnish (FIN) AF: 0.668 AC: 7042 AN: 10542

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45502 AN: 67976

Other (OTH) AF: 0.622 AC: 1313 AN: 2110

Alfa AF: 0.633 Hom.: 3862

Bravo AF: 0.587

Asia WGS AF: 0.530 AC: 1842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.5
DANN	Benign	0.53
PhyloP100		0.76
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: rs7123797; hg19: chr11-113262571;