12-99939037-C-T

Variant names:

• chr12-99939037-C-T
• rs2373201
• NM_001352186.2:c.134+45067G>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.134+45067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,030 control chromosomes in the GnomAD database, including 3,926 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 0.22 (3926 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.134+45067G>A		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.134+45067G>A		intron_variant	Intron 1 of 26		NM_001352186.2	ENSP00000508105.1
ANKS1B	ENST00000547776.6	c.134+45067G>A		intron_variant	Intron 1 of 25	1		ENSP00000449629.2
ANKS1B	ENST00000547010.5	c.-133+45067G>A		intron_variant	Intron 1 of 17	1		ENSP00000448512.1
ANKS1B	ENST00000549866.5	c.134+45067G>A		intron_variant	Intron 1 of 11	2		ENSP00000449894.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33351 AN: 151912 Hom.: 3923 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.219 AC: 33365 AN: 152030 Hom.: 3926 Cov.: 32 AF XY: 0.213 AC XY: 15866 AN XY: 74330

African (AFR) AF: 0.269 AC: 11148 AN: 41450

American (AMR) AF: 0.147 AC: 2241 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.137 AC: 658 AN: 4816

European-Finnish (FIN) AF: 0.211 AC: 2232 AN: 10584

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15922 AN: 67948

Other (OTH) AF: 0.193 AC: 409 AN: 2114

Alfa AF: 0.227 Hom.: 2196

Bravo AF: 0.215

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.96
DANN	Benign	0.15
PhyloP100		-0.046
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: rs2373201; hg19: chr12-100332815;