chr12-99216760-T-A

Variant names:

• chr12-99216760-T-A
• rs10507113
• NM_001352186.2:c.2419+27582A>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.2419+27582A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,258 control chromosomes in the GnomAD database, including 805 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 0.071 (805 hom., cov: 33)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2419+27582A>T		intron_variant	Intron 14 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2419+27582A>T		intron_variant	Intron 14 of 26		NM_001352186.2	ENSP00000508105.1
ANKS1B	ENST00000547776.6	c.2419+27582A>T		intron_variant	Intron 14 of 25	1		ENSP00000449629.2
ANKS1B	ENST00000547010.5	c.1147+27594A>T		intron_variant	Intron 7 of 17	1		ENSP00000448512.1
ANKS1B	ENST00000550778.5	c.232+27582A>T		intron_variant	Intron 2 of 13	1		ENSP00000448744.1

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10811 AN: 152140 Hom.: 802 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0712 AC: 10836 AN: 152258 Hom.: 805 Cov.: 33 AF XY: 0.0696 AC XY: 5180 AN XY: 74470

African (AFR) AF: 0.191 AC: 7909 AN: 41508

American (AMR) AF: 0.0398 AC: 609 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

East Asian (EAS) AF: 0.118 AC: 613 AN: 5180

South Asian (SAS) AF: 0.104 AC: 504 AN: 4824

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10626

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 871 AN: 68026

Other (OTH) AF: 0.0633 AC: 134 AN: 2116

Alfa AF: 0.0396 Hom.: 61

Bravo AF: 0.0785

Asia WGS AF: 0.118 AC: 410 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		0.30
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: rs10507113; hg19: chr12-99610538;