rs10492272

Variant names:

• chr12-98871370-C-A
• rs10492272
• NM_001352186.2:c.2779-39234G>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.2779-39234G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,150 control chromosomes in the GnomAD database, including 504 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 0.075 (504 hom., cov: 33)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2779-39234G>T		intron_variant	Intron 17 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2779-39234G>T		intron_variant	Intron 17 of 26		NM_001352186.2	ENSP00000508105.1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11356 AN: 152032 Hom.: 504 Cov.: 33

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0600

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0747 AC: 11364 AN: 152150 Hom.: 504 Cov.: 33 AF XY: 0.0741 AC XY: 5516 AN XY: 74404

African (AFR) AF: 0.0436 AC: 1808 AN: 41512

American (AMR) AF: 0.0599 AC: 916 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 329 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4828

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10570

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0984 AC: 6687 AN: 67974

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0783 Hom.: 152

Bravo AF: 0.0694

Asia WGS AF: 0.0120 AC: 44 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.61
PhyloP100		0.24
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: rs10492272; hg19: chr12-99265148;