12-98944566-T-G

Position:

• chr12-98944566-T-G

Variant summary

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

The NM_001352186.2(ANKS1B):​c.2778+108591A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,114 control chromosomes in the GnomAD database, including 57,122 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 0.86 (57122 hom., cov: 31)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2778+108591A>C		intron_variant		ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2778+108591A>C		intron_variant			NM_001352186.2	ENSP00000508105	P1
	ENST00000551372.1	n.44-5153T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131075 AN: 151996 Hom.: 57076 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.862 AC: 131181 AN: 152114 Hom.: 57122 Cov.: 31 AF XY: 0.865 AC XY: 64336 AN XY: 74382

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.917

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.880

Alfa AF: 0.903 Hom.: 77954

Bravo AF: 0.858

Asia WGS AF: 0.845 AC: 2940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.44

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: rs616804; hg19: chr12-99338344;