ENST00000547776.6:c.3673-2700A>G

Variant names:

• chr12-98738334-T-C
• rs17028658
• ENST00000547776.6:c.3673-2700A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000547776.6(ANKS1B):​c.3673-2700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,246 control chromosomes in the GnomAD database, including 633 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 0.078 (633 hom., cov: 33)
• Consequence: ANKS1B ENST00000547776.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_152788.4	c.3673-2700A>G		intron_variant	Intron 25 of 25		NP_690001.3
ANKS1B	NM_001352196.2	c.1423-2700A>G		intron_variant	Intron 12 of 12		NP_001339125.1
ANKS1B	NM_001352197.2	c.1351-2700A>G		intron_variant	Intron 11 of 11		NP_001339126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000547776.6	c.3673-2700A>G		intron_variant	Intron 25 of 25	1		ENSP00000449629.2
ANKS1B	ENST00000547010.5	c.2221-2700A>G		intron_variant	Intron 17 of 17	1		ENSP00000448512.1
ANKS1B	ENST00000549558.6	c.1171-2700A>G		intron_variant	Intron 10 of 10	1		ENSP00000448993.2

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11852 AN: 152126 Hom.: 634 Cov.: 33

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0777 AC: 11833 AN: 152246 Hom.: 633 Cov.: 33 AF XY: 0.0824 AC XY: 6130 AN XY: 74430

African (AFR) AF: 0.0158 AC: 657 AN: 41576

American (AMR) AF: 0.100 AC: 1531 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1354 AN: 5152

South Asian (SAS) AF: 0.182 AC: 878 AN: 4822

European-Finnish (FIN) AF: 0.105 AC: 1110 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0830 AC: 5648 AN: 68010

Other (OTH) AF: 0.0734 AC: 155 AN: 2112

Alfa AF: 0.0810 Hom.: 71

Bravo AF: 0.0729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.71
PhyloP100		0.22
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: rs17028658; hg19: chr12-99132112;