rs483610

chr12-98940751-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.2779-108615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,028 control chromosomes in the GnomAD database, including 31,791 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 (31791 hom., cov: 32)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1B	NM_001352186.2	c.2779-108615G>A		intron_variant		ENST00000683438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2779-108615G>A		intron_variant			NM_001352186.2	P1
	ENST00000551372.1	n.44-8968C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93133 AN: 151910 Hom.: 31792 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.613 AC: 93137 AN: 152028 Hom.: 31791 Cov.: 32 AF XY: 0.615 AC XY: 45689 AN XY: 74300

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.630

Alfa AF: 0.727 Hom.: 54906

Bravo AF: 0.589

Asia WGS AF: 0.548 AC: 1904 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.33
Dann	Benign	0.42

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: rs483610; hg19: chr12-99334529;