chr12-98944566-T-G

Variant names:

• chr12-98944566-T-G
• rs616804
• NM_001352186.2:c.2778+108591A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352186.2(ANKS1B):​c.2778+108591A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,114 control chromosomes in the GnomAD database, including 57,122 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 0.86 (57122 hom., cov: 31)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 0 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.903 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.2778+108591A>C		intron	N/A	NP_001339115.1	A0A804HKX1
	ANKS1B	NM_001352188.1		c.2778+108591A>C		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.2778+108591A>C		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.2778+108591A>C		intron	N/A	ENSP00000508105.1	A0A804HKX1
	ANKS1B	ENST00000547776.6	TSL:1	c.2778+108591A>C		intron	N/A	ENSP00000449629.2	Q7Z6G8-1
	ANKS1B	ENST00000547010.5	TSL:1	c.1506+108591A>C		intron	N/A	ENSP00000448512.1	Q7Z6G8-6

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131075 AN: 151996 Hom.: 57076 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.862 AC: 131181 AN: 152114 Hom.: 57122 Cov.: 31 AF XY: 0.865 AC XY: 64336 AN XY: 74382

African (AFR) AF: 0.739 AC: 30615 AN: 41448

American (AMR) AF: 0.913 AC: 13957 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3182 AN: 3470

East Asian (EAS) AF: 0.901 AC: 4667 AN: 5182

South Asian (SAS) AF: 0.827 AC: 3983 AN: 4816

European-Finnish (FIN) AF: 0.940 AC: 9948 AN: 10586

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.909 AC: 61835 AN: 68014

Other (OTH) AF: 0.880 AC: 1856 AN: 2108

Alfa AF: 0.897 Hom.: 108583

Bravo AF: 0.858

Asia WGS AF: 0.845 AC: 2940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.44
PhyloP100		0.29
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: rs616804; hg19: chr12-99338344;