rs7132927

chr12-99903864-C-A

Variant summary

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

The NM_001352186.2(ANKS1B):c.135-78475G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,706 control chromosomes in the GnomAD database, including 19,214 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 0.49 (19214 hom., cov: 30)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1B	NM_001352186.2	c.135-78475G>T		intron_variant		ENST00000683438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1B	ENST00000683438.2	c.135-78475G>T		intron_variant			NM_001352186.2	P1
ANKS1B	ENST00000547010.5	c.-133+80240G>T		intron_variant		1
ANKS1B	ENST00000547776.6	c.135-78475G>T		intron_variant		1
ANKS1B	ENST00000549866.5	c.135-78475G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74640 AN: 151588 Hom.: 19201 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.492 AC: 74688 AN: 151706 Hom.: 19214 Cov.: 30 AF XY: 0.482 AC XY: 35688 AN XY: 74112

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.0684

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.472

Alfa AF: 0.539 Hom.: 10140

Bravo AF: 0.486

Asia WGS AF: 0.309 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.59
Dann	Benign	0.47

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: rs7132927; hg19: chr12-100297642;