rs2063508

Variant names:

• chr12-99530773-C-T
• rs2063508
• NM_001352186.2:c.1273-26132G>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.1273-26132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,956 control chromosomes in the GnomAD database, including 15,863 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 0.45 (15863 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 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.1273-26132G>A		intron	N/A	NP_001339115.1
	ANKS1B	NM_001352188.1		c.1273-26132G>A		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.1273-26132G>A		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.1273-26132G>A		intron	N/A	ENSP00000508105.1
	ANKS1B	ENST00000547776.6	TSL:1	c.1273-26132G>A		intron	N/A	ENSP00000449629.2
	ANKS1B	ENST00000547010.5	TSL:1	c.13-26132G>A		intron	N/A	ENSP00000448512.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68979 AN: 151838 Hom.: 15829 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.455 AC: 69066 AN: 151956 Hom.: 15863 Cov.: 32 AF XY: 0.455 AC XY: 33805 AN XY: 74258

African (AFR) AF: 0.463 AC: 19182 AN: 41406

American (AMR) AF: 0.439 AC: 6699 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3468

East Asian (EAS) AF: 0.548 AC: 2831 AN: 5166

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4818

European-Finnish (FIN) AF: 0.450 AC: 4753 AN: 10552

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 31011 AN: 67958

Other (OTH) AF: 0.418 AC: 882 AN: 2112

Alfa AF: 0.448 Hom.: 10846

Bravo AF: 0.459

Asia WGS AF: 0.433 AC: 1500 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.20
PhyloP100		0.013
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: rs2063508; hg19: chr12-99924551;