chr12-98940751-C-T

Variant names:

• chr12-98940751-C-T
• rs483610
• NM_001352186.2:c.2779-108615G>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.2779-108615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,028 control chromosomes in the GnomAD database, including 31,791 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 0.61 (31791 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 5 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

ENSG00000257458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 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.2779-108615G>A		intron	N/A	NP_001339115.1	A0A804HKX1
	ANKS1B	NM_001352188.1		c.2779-108615G>A		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.2779-108615G>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.2779-108615G>A		intron	N/A	ENSP00000508105.1	A0A804HKX1
	ANKS1B	ENST00000547776.6	TSL:1	c.2779-108615G>A		intron	N/A	ENSP00000449629.2	Q7Z6G8-1
	ANKS1B	ENST00000547010.5	TSL:1	c.1507-108615G>A		intron	N/A	ENSP00000448512.1	Q7Z6G8-6

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93133 AN: 151910 Hom.: 31792 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.613 AC: 93137 AN: 152028 Hom.: 31791 Cov.: 32 AF XY: 0.615 AC XY: 45689 AN XY: 74300

African (AFR) AF: 0.294 AC: 12174 AN: 41416

American (AMR) AF: 0.635 AC: 9699 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2739 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3103 AN: 5164

South Asian (SAS) AF: 0.600 AC: 2892 AN: 4820

European-Finnish (FIN) AF: 0.792 AC: 8391 AN: 10590

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51874 AN: 67976

Other (OTH) AF: 0.630 AC: 1329 AN: 2108

Alfa AF: 0.684 Hom.: 78444

Bravo AF: 0.589

Asia WGS AF: 0.548 AC: 1904 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.42
PhyloP100		-2.0
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: rs483610; hg19: chr12-99334529;