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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKK1	NM_178510.2 link	c.480+147T>C		intron_variant	Intron 2 of 7	ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4 link	c.480+147T>C		intron_variant	Intron 2 of 7	1	NM_178510.2	ENSP00000306678.3
ANKK1	ENST00000542948.1 link	n.141+147T>C		intron_variant	Intron 1 of 4	3		ENSP00000445810.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over