rs201400

Variant names:

• chr12-98840522-G-A
• rs201400
• NM_001352186.2:c.2779-8386C>T

Variant summary

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

The NM_001352186.2(ANKS1B):​c.2779-8386C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,008 control chromosomes in the GnomAD database, including 28,842 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 0.61 (28842 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2779-8386C>T		intron_variant	Intron 17 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2779-8386C>T		intron_variant	Intron 17 of 26		NM_001352186.2	ENSP00000508105.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92921 AN: 151890 Hom.: 28821 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.612 AC: 92990 AN: 152008 Hom.: 28842 Cov.: 32 AF XY: 0.615 AC XY: 45698 AN XY: 74300

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.603

Alfa AF: 0.571 Hom.: 13394

Bravo AF: 0.615

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.75

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: rs201400; hg19: chr12-99234300;