rs4938015

Positions:

• chr11-113393922-T-C

Variant summary

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

The NM_178510.2(ANKK1):​c.480+147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 996,402 control chromosomes in the GnomAD database, including 198,945 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 0.58 (26531 hom., cov: 32)
  • Exomes 𝑓: 0.63 (172414 hom.)
• Consequence: ANKK1 NM_178510.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKK1	NM_178510.2	c.480+147T>C		intron_variant		ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4	c.480+147T>C		intron_variant		1	NM_178510.2	ENSP00000306678.3
ANKK1	ENST00000542948.1	n.141+147T>C		intron_variant		3		ENSP00000445810.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88073 AN: 151948 Hom.: 26527 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.635 AC: 535850 AN: 844336 Hom.: 172414 AF XY: 0.634 AC XY: 266880 AN XY: 420864

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.680

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.579 AC: 88112 AN: 152066 Hom.: 26531 Cov.: 32 AF XY: 0.578 AC XY: 42996 AN XY: 74344

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.605

Alfa AF: 0.604 Hom.: 4530

Bravo AF: 0.562

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.1
DANN	Benign	0.80

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: rs4938015; hg19: chr11-113264644;