chr12-99880552-G-A

Variant names:

• chr12-99880552-G-A
• rs10745877
• NM_001352186.2:c.135-55163C>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.135-55163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,980 control chromosomes in the GnomAD database, including 32,826 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 0.64 (32826 hom., cov: 31)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1B	NM_001352186.2	MANE Select	c.135-55163C>T		intron	N/A	NP_001339115.1
	ANKS1B	NM_001352188.1		c.135-55163C>T		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.135-55163C>T		intron	N/A	NP_001339116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1B	ENST00000683438.2	MANE Select	c.135-55163C>T		intron	N/A	ENSP00000508105.1
	ANKS1B	ENST00000547776.6	TSL:1	c.135-55163C>T		intron	N/A	ENSP00000449629.2
	ANKS1B	ENST00000547010.5	TSL:1	c.-133+103552C>T		intron	N/A	ENSP00000448512.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97510 AN: 151862 Hom.: 32800 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.642 AC: 97593 AN: 151980 Hom.: 32826 Cov.: 31 AF XY: 0.627 AC XY: 46604 AN XY: 74274

African (AFR) AF: 0.770 AC: 31929 AN: 41476

American (AMR) AF: 0.544 AC: 8312 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2015 AN: 3462

East Asian (EAS) AF: 0.0689 AC: 356 AN: 5170

South Asian (SAS) AF: 0.471 AC: 2262 AN: 4800

European-Finnish (FIN) AF: 0.564 AC: 5940 AN: 10534

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44609 AN: 67958

Other (OTH) AF: 0.615 AC: 1296 AN: 2108

Alfa AF: 0.642 Hom.: 16004

Bravo AF: 0.646

Asia WGS AF: 0.354 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.4
DANN	Benign	0.62
PhyloP100		0.65
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: rs10745877; hg19: chr12-100274330;