chr12-99104409-C-T

Variant names:

• chr12-99104409-C-T
• rs10860392
• NM_001352186.2:c.2527-19386G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ANKS1B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000258039 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352186.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1B	NM_001352186.2	MANE Select	c.2527-19386G>A		intron	N/A	NP_001339115.1
	ANKS1B	NM_001352188.1		c.2527-19386G>A		intron	N/A	NP_001339117.1
	ANKS1B	NM_001352187.1		c.2527-19386G>A		intron	N/A	NP_001339116.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS1B	ENST00000683438.2	MANE Select	c.2527-19386G>A		intron	N/A	ENSP00000508105.1
	ANKS1B	ENST00000547776.6	TSL:1	c.2527-19386G>A		intron	N/A	ENSP00000449629.2
	ANKS1B	ENST00000547010.5	TSL:1	c.1255-19386G>A		intron	N/A	ENSP00000448512.1

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

African (AFR) AF: 0.657 AC: 27265 AN: 41480

American (AMR) AF: 0.740 AC: 11317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1999 AN: 3464

East Asian (EAS) AF: 0.889 AC: 4589 AN: 5164

South Asian (SAS) AF: 0.639 AC: 3074 AN: 4812

European-Finnish (FIN) AF: 0.636 AC: 6718 AN: 10556

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42613 AN: 67958

Other (OTH) AF: 0.634 AC: 1342 AN: 2116

Alfa AF: 0.638 Hom.: 60591

Bravo AF: 0.666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.55
DANN	Benign	0.36
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10860392; hg19: chr12-99498187;