rs1554547

Positions:

• chr12-98974370-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.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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.2778+78787G>A		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+78787G>A		intron_variant			NM_001352186.2	ENSP00000508105	P1
	ENST00000551372.1	n.248-2022C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0350 Hom.: 453

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

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: rs1554547; hg19: chr12-99368148;