chr12-99104409-C-T

Position:

• chr12-99104409-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.2527-19386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,042 control chromosomes in the GnomAD database, including 32,961 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 0.66 (32961 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2527-19386G>A		intron_variant		ENST00000683438.2	NP_001339115.1
LOC101928937	NR_110095.1	n.550-114C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2527-19386G>A		intron_variant			NM_001352186.2	ENSP00000508105	P1
	ENST00000547633.2	n.550-114C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99637 AN: 151924 Hom.: 32909 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.656 AC: 99739 AN: 152042 Hom.: 32961 Cov.: 32 AF XY: 0.658 AC XY: 48935 AN XY: 74316

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.634

Alfa AF: 0.629 Hom.: 34917

Bravo AF: 0.666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.55
DANN	Benign	0.36

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: rs10860392; hg19: chr12-99498187;