chr12-98745774-C-T

Variant names:

• chr12-98745774-C-T
• rs752252888
• NM_001352186.2:c.3823G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001352186.2(ANKS1B):​c.3823G>A​(p.Gly1275Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000967 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000095 (0 hom.)
• Consequence: ANKS1B NM_001352186.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.69

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09810454).
• BP6: Variant 12-98745774-C-T is Benign according to our data. Variant chr12-98745774-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 738742.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS1B	NM_001352186.2	c.3823G>A	p.Gly1275Ser	missense_variant	Exon 27 of 27	ENST00000683438.2	NP_001339115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS1B	ENST00000683438.2	c.3823G>A	p.Gly1275Ser	missense_variant	Exon 27 of 27		NM_001352186.2	ENSP00000508105.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000848 AC: 21 AN: 247610 AF XY: 0.000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000951 AC: 139 AN: 1461454 Hom.: 0 Cov.: 33 AF XY: 0.000106 AC XY: 77 AN XY: 726998

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33438

Gnomad4 AMR exome AF: 0.0000671 AC: 3 AN: 44706

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26126

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39686

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86216

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53376

Gnomad4 NFE exome AF: 0.000116 AC: 129 AN: 1111770

Gnomad4 Remaining exome AF: 0.0000828 AC: 5 AN: 60368

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74502

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000250 AC: 0.000249882 AN: 0.000249882

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000267 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.098	T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
PROVEAN	Benign	0.31	N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		1.0	D;.;D;.;D;B
Vest4		0.20
MVP		0.72
ClinPred		0.084	T
GERP RS		3.8
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs752252888; hg19: chr12-99139552;