12-99903864-C-A

Variant names:

• chr12-99903864-C-A
• rs7132927
• NM_001352186.2:c.135-78475G>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.135-78475G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,706 control chromosomes in the GnomAD database, including 19,214 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 0.49 (19214 hom., cov: 30)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.135-78475G>T		intron_variant	Intron 1 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.135-78475G>T		intron_variant	Intron 1 of 26		NM_001352186.2	ENSP00000508105.1
ANKS1B	ENST00000547776.6	c.135-78475G>T		intron_variant	Intron 1 of 25	1		ENSP00000449629.2
ANKS1B	ENST00000547010.5	c.-133+80240G>T		intron_variant	Intron 1 of 17	1		ENSP00000448512.1
ANKS1B	ENST00000549866.5	c.135-78475G>T		intron_variant	Intron 1 of 11	2		ENSP00000449894.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74640 AN: 151588 Hom.: 19201 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.492 AC: 74688 AN: 151706 Hom.: 19214 Cov.: 30 AF XY: 0.482 AC XY: 35688 AN XY: 74112

African (AFR) AF: 0.458 AC: 18909 AN: 41306

American (AMR) AF: 0.431 AC: 6575 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1763 AN: 3464

East Asian (EAS) AF: 0.0684 AC: 353 AN: 5162

South Asian (SAS) AF: 0.417 AC: 2001 AN: 4804

European-Finnish (FIN) AF: 0.471 AC: 4933 AN: 10476

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38505 AN: 67930

Other (OTH) AF: 0.472 AC: 998 AN: 2116

Alfa AF: 0.539 Hom.: 11361

Bravo AF: 0.486

Asia WGS AF: 0.309 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.47
PhyloP100		-1.7
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: rs7132927; hg19: chr12-100297642;