12-99898943-C-A

Position:

• chr12-99898943-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.135-73554G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,962 control chromosomes in the GnomAD database, including 20,722 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 0.51 (20722 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.135-73554G>T		intron_variant		ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.135-73554G>T		intron_variant			NM_001352186.2	ENSP00000508105	P1
ANKS1B	ENST00000547010.5	c.-133+85161G>T		intron_variant		1		ENSP00000448512
ANKS1B	ENST00000547776.6	c.135-73554G>T		intron_variant		1		ENSP00000449629
ANKS1B	ENST00000549866.5	c.135-73554G>T		intron_variant		2		ENSP00000449894

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77703 AN: 151844 Hom.: 20698 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.512 AC: 77770 AN: 151962 Hom.: 20722 Cov.: 32 AF XY: 0.500 AC XY: 37153 AN XY: 74264

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.0617

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.488

Alfa AF: 0.529 Hom.: 29710

Bravo AF: 0.512

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.46

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: rs11110099; hg19: chr12-100292721;