chr12-99915350-A-G

Variant names:

• chr12-99915350-A-G
• rs17029861
• NM_001352186.2:c.134+68754T>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.134+68754T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,054 control chromosomes in the GnomAD database, including 3,096 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 0.19 (3096 hom., cov: 31)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 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.134+68754T>C		intron	N/A	NP_001339115.1
	ANKS1B	NM_001352188.1		c.134+68754T>C		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.134+68754T>C		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.134+68754T>C		intron	N/A	ENSP00000508105.1
	ANKS1B	ENST00000547776.6	TSL:1	c.134+68754T>C		intron	N/A	ENSP00000449629.2
	ANKS1B	ENST00000547010.5	TSL:1	c.-133+68754T>C		intron	N/A	ENSP00000448512.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29494 AN: 151942 Hom.: 3095 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.194 AC: 29506 AN: 152054 Hom.: 3096 Cov.: 31 AF XY: 0.189 AC XY: 14031 AN XY: 74338

African (AFR) AF: 0.175 AC: 7252 AN: 41474

American (AMR) AF: 0.138 AC: 2108 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.137 AC: 660 AN: 4806

European-Finnish (FIN) AF: 0.210 AC: 2218 AN: 10566

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16146 AN: 67954

Other (OTH) AF: 0.174 AC: 366 AN: 2108

Alfa AF: 0.216 Hom.: 12054

Bravo AF: 0.185

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.68
PhyloP100		0.87
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: rs17029861; hg19: chr12-100309128;