rs4590907

Positions:

• chr11-113392648-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178510.2(ANKK1):​c.186-833T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,192 control chromosomes in the GnomAD database, including 4,058 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 0.21 (4058 hom., cov: 33)
• Consequence: ANKK1 NM_178510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKK1	NM_178510.2	c.186-833T>G		intron_variant		ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4	c.186-833T>G		intron_variant		1	NM_178510.2	ENSP00000306678	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31977 AN: 152074 Hom.: 4045 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.210 AC: 32029 AN: 152192 Hom.: 4058 Cov.: 33 AF XY: 0.217 AC XY: 16138 AN XY: 74418

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.183

Alfa AF: 0.155 Hom.: 990

Bravo AF: 0.213

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.13
DANN	Benign	0.90

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: rs4590907; hg19: chr11-113263370;