rs201403

Variant names:

• chr12-98836731-G-A
• rs201403
• NM_001352186.2:c.2779-4595C>T

Variant summary

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

The NM_001352186.2(ANKS1B):​c.2779-4595C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,882 control chromosomes in the GnomAD database, including 18,363 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 0.48 (18363 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352186.2. 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
	ANKS1B	NM_001352186.2	MANE Select	c.2779-4595C>T		intron	N/A	NP_001339115.1	A0A804HKX1
	ANKS1B	NM_001352188.1		c.2779-4595C>T		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.2779-4595C>T		intron	N/A	NP_001339116.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1B	ENST00000683438.2	MANE Select	c.2779-4595C>T		intron	N/A	ENSP00000508105.1	A0A804HKX1
	ANKS1B	ENST00000547776.6	TSL:1	c.2779-4595C>T		intron	N/A	ENSP00000449629.2	Q7Z6G8-1
	ANKS1B	ENST00000547010.5	TSL:1	c.1507-4595C>T		intron	N/A	ENSP00000448512.1	Q7Z6G8-6

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73502 AN: 151764 Hom.: 18363 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.484 AC: 73523 AN: 151882 Hom.: 18363 Cov.: 32 AF XY: 0.490 AC XY: 36366 AN XY: 74226

African (AFR) AF: 0.363 AC: 15046 AN: 41408

American (AMR) AF: 0.508 AC: 7764 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3466

East Asian (EAS) AF: 0.718 AC: 3708 AN: 5164

South Asian (SAS) AF: 0.638 AC: 3067 AN: 4806

European-Finnish (FIN) AF: 0.527 AC: 5551 AN: 10526

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35023 AN: 67924

Other (OTH) AF: 0.499 AC: 1051 AN: 2106

Alfa AF: 0.504 Hom.: 28732

Bravo AF: 0.476

Asia WGS AF: 0.649 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		0.40
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: rs201403; hg19: chr12-99230509;