12-99510762-A-T

Variant names:

• chr12-99510762-A-T
• rs1961649
• NM_001352186.2:c.1273-6121T>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.1273-6121T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,064 control chromosomes in the GnomAD database, including 807 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 0.086 (807 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.1273-6121T>A		intron_variant	Intron 9 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.1273-6121T>A		intron_variant	Intron 9 of 26		NM_001352186.2	ENSP00000508105.1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13127 AN: 151946 Hom.: 807 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0863 AC: 13128 AN: 152064 Hom.: 807 Cov.: 32 AF XY: 0.0865 AC XY: 6429 AN XY: 74332

African (AFR) AF: 0.0214 AC: 889 AN: 41528

American (AMR) AF: 0.0667 AC: 1016 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.157 AC: 1664 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8774 AN: 67916

Other (OTH) AF: 0.0804 AC: 170 AN: 2114

Alfa AF: 0.0525 Hom.: 49

Bravo AF: 0.0783

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		-0.61
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: rs1961649; hg19: chr12-99904540;