dbSNP rs4938015: ANKK1:c.480+147T>C (chr11-113393922-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.121

Publications

24 publications found

Variant links:

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]

ANKK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178510.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKK1	NM_178510.2	MANE Select	c.480+147T>C		intron	N/A	NP_848605.1	Q8NFD2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKK1	ENST00000303941.4	TSL:1 MANE Select	c.480+147T>C		intron	N/A	ENSP00000306678.3	Q8NFD2
	ANKK1	ENST00000542948.1	TSL:3	n.141+147T>C		intron	N/A	ENSP00000445810.1	H0YH32

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88073

AN:

151948

Hom.:

26527

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.392

AC:

7928

AN:

20212

American (AMR)

AF:

0.534

AC:

9862

AN:

18478

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

10879

AN:

16102

East Asian (EAS)

AF:

0.586

AC:

19178

AN:

32728

South Asian (SAS)

AF:

0.582

AC:

30561

AN:

52550

European-Finnish (FIN)

AF:

0.680

AC:

20920

AN:

30746

Middle Eastern (MID)

AF:

0.613

AC:

1710

AN:

2790

European-Non Finnish (NFE)

AF:

0.649

AC:

410130

AN:

631606

Other (OTH)

AF:

0.631

AC:

24682

AN:

39124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

9014

18028

27042

36056

45070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9044

18088

27132

36176

45220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.579

AC:

88112

AN:

152066

Hom.:

26531

Cov.:

AF XY:

0.578

AC XY:

42996

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.416

AC:

17263

AN:

41460

American (AMR)

AF:

0.541

AC:

8259

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2316

AN:

3470

East Asian (EAS)

AF:

0.565

AC:

2918

AN:

5168

South Asian (SAS)

AF:

0.569

AC:

2745

AN:

4828

European-Finnish (FIN)

AF:

0.667

AC:

7049

AN:

10562

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.668

AC:

45390

AN:

67986

Other (OTH)

AF:

0.605

AC:

1279

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1840

3680

5521

7361

9201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.599

Hom.:

4612

Bravo

AF:

0.562

Asia WGS

AF:

0.527

AC:

1831

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.1

(source)

DANN

Benign

0.80

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over