NM_001352186.2:c.3342+2340G>A

Variant names:

• chr12-98796594-C-T
• rs2036225
• NM_001352186.2:c.3342+2340G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352186.2(ANKS1B):​c.3342+2340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,960 control chromosomes in the GnomAD database, including 13,133 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 0.39 (13133 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 6 publications found

Genes affected

ANKS1B (HGNC:24600): (ankyrin repeat and sterile alpha motif domain containing 1B) This gene encodes a multi-domain protein that is predominantly expressed in brain and testis. This protein interacts with amyloid beta protein precursor (AbetaPP) and may have a role in normal brain development, and in the pathogenesis of Alzheimer's disease. Expression of this gene has been shown to be elevated in patients with pre-B cell acute lymphocytic leukemia associated with t(1;19) translocation. Alternatively spliced transcript variants encoding different isoforms (some with different subcellular localization, PMID:15004329) have been described for this gene. [provided by RefSeq, Aug 2011]

ANKS1B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.3342+2340G>A		intron_variant	Intron 22 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.3342+2340G>A		intron_variant	Intron 22 of 26		NM_001352186.2	ENSP00000508105.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59203 AN: 151842 Hom.: 13124 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.390 AC: 59260 AN: 151960 Hom.: 13133 Cov.: 32 AF XY: 0.403 AC XY: 29946 AN XY: 74252

African (AFR) AF: 0.195 AC: 8075 AN: 41476

American (AMR) AF: 0.524 AC: 7996 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1519 AN: 3468

East Asian (EAS) AF: 0.728 AC: 3757 AN: 5162

South Asian (SAS) AF: 0.600 AC: 2892 AN: 4824

European-Finnish (FIN) AF: 0.502 AC: 5282 AN: 10528

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28308 AN: 67926

Other (OTH) AF: 0.414 AC: 874 AN: 2110

Alfa AF: 0.397 Hom.: 12388

Bravo AF: 0.382

Asia WGS AF: 0.622 AC: 2165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2036225; hg19: chr12-99190372;