rs1492254

Positions:

• chr12-99305506-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352186.2(ANKS1B):​c.1757-58642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,836 control chromosomes in the GnomAD database, including 19,554 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 0.47 (19554 hom., cov: 31)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1B	NM_001352186.2	c.1757-58642G>A		intron_variant		ENST00000683438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1B	ENST00000683438.2	c.1757-58642G>A		intron_variant			NM_001352186.2	P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71961 AN: 151716 Hom.: 19513 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.474 AC: 72045 AN: 151836 Hom.: 19554 Cov.: 31 AF XY: 0.468 AC XY: 34747 AN XY: 74208

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.452

Alfa AF: 0.445 Hom.: 2437

Bravo AF: 0.485

Asia WGS AF: 0.481 AC: 1668 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1492254; hg19: chr12-99699284;