rs7118900

Variant names:

• chr11-113396099-G-A
• rs7118900
• NM_178510.2:c.715G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-113396099-G-A
• chr11-113396099-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_178510.2(ANKK1):​c.715G>A​(p.Ala239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,613,786 control chromosomes in the GnomAD database, including 39,971 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (5101 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34870 hom.)
• Consequence: ANKK1 NM_178510.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.00
• Publications: 62 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 -9 ACMG points.

• BP6: Variant 11-113396099-G-A is Benign according to our data. Variant chr11-113396099-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060698.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 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.715G>A	p.Ala239Thr	missense	Exon 5 of 8	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.715G>A	p.Ala239Thr	missense	Exon 5 of 8	ENSP00000306678.3	Q8NFD2
	ANKK1	ENST00000542948.1	TSL:3	n.*269G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000445810.1	H0YH32
	ANKK1	ENST00000542948.1	TSL:3	n.*269G>A		3_prime_UTR	Exon 5 of 5	ENSP00000445810.1	H0YH32

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37472 AN: 152018 Hom.: 5089 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.253 AC: 63155 AN: 249136 AF XY: 0.243

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.449

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.398

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.208 AC: 304222 AN: 1461650 Hom.: 34870 Cov.: 35 AF XY: 0.208 AC XY: 151413 AN XY: 727116

African (AFR) AF: 0.313 AC: 10488 AN: 33478

American (AMR) AF: 0.428 AC: 19156 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3479 AN: 26134

East Asian (EAS) AF: 0.384 AC: 15255 AN: 39700

South Asian (SAS) AF: 0.274 AC: 23667 AN: 86254

European-Finnish (FIN) AF: 0.183 AC: 9752 AN: 53378

Middle Eastern (MID) AF: 0.153 AC: 880 AN: 5768

European-Non Finnish (NFE) AF: 0.188 AC: 208936 AN: 1111844

Other (OTH) AF: 0.209 AC: 12609 AN: 60374

GnomAD4 genome AF: 0.247 AC: 37519 AN: 152136 Hom.: 5101 Cov.: 32 AF XY: 0.249 AC XY: 18554 AN XY: 74374

African (AFR) AF: 0.324 AC: 13430 AN: 41484

American (AMR) AF: 0.321 AC: 4906 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2043 AN: 5150

South Asian (SAS) AF: 0.285 AC: 1377 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2060 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12501 AN: 68004

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.205 Hom.: 16531

Bravo AF: 0.262

TwinsUK AF: 0.186 AC: 690

ALSPAC AF: 0.176 AC: 680

ESP6500AA AF: 0.308 AC: 1246

ESP6500EA AF: 0.182 AC: 1518

ExAC AF: 0.246 AC: 29698

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ANKK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.96
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.00050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Benign	0.11	T
Sift4G	Uncertain	0.039	D
Polyphen		0.15	B
Vest4		0.099
MPC		0.068
ClinPred		0.018	T
GERP RS		2.5
Varity_R		0.033
gMVP		0.26
Mutation Taster		=80/20	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7118900; hg19: chr11-113266821; COSMIC: COSV58270310;