rs1554547

Variant names:

• chr12-98974370-C-T
• rs1554547
• NM_001352186.2:c.2778+78787G>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.2778+78787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,072 control chromosomes in the GnomAD database, including 1,480 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 0.098 (1480 hom., cov: 31)
• Consequence: ANKS1B NM_001352186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 2 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

ENSG00000257458 (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 (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2778+78787G>A		intron_variant	Intron 17 of 26	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.2778+78787G>A		intron_variant	Intron 17 of 26		NM_001352186.2	ENSP00000508105.1

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14882 AN: 151954 Hom.: 1465 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0723

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

GnomAD4 genome AF: 0.0983 AC: 14950 AN: 152072 Hom.: 1480 Cov.: 31 AF XY: 0.103 AC XY: 7641 AN XY: 74346

African (AFR) AF: 0.243 AC: 10077 AN: 41450

American (AMR) AF: 0.0970 AC: 1482 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3466

East Asian (EAS) AF: 0.0579 AC: 300 AN: 5182

South Asian (SAS) AF: 0.241 AC: 1162 AN: 4818

European-Finnish (FIN) AF: 0.0609 AC: 643 AN: 10566

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 977 AN: 67996

Other (OTH) AF: 0.0749 AC: 158 AN: 2110

Alfa AF: 0.0444 Hom.: 1596

Bravo AF: 0.104

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.0
DANN	Benign	0.45
PhyloP100		0.31
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: rs1554547; hg19: chr12-99368148;