rs2304880

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000037.4(ANK1):c.2349C>T(p.Thr783Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,613,882 control chromosomes in the GnomAD database, including 57,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4343 hom., cov: 33)

Exomes 𝑓: 0.26 ( 52962 hom. )

Consequence

ANK1
NM_000037.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.976

Variant links:

Genes affected

ANK1 (HGNC:492): (ankyrin 1) Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. [provided by RefSeq, Dec 2008]

ANK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 8-41702091-G-A is Benign according to our data. Variant chr8-41702091-G-A is described in ClinVar as [Benign]. Clinvar id is 261299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-41702091-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK1	NM_000037.4 link	c.2349C>T	p.Thr783Thr	synonymous_variant	Exon 21 of 43	ENST00000289734.13	NP_000028.3	P16157-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK1	ENST00000289734.13 link	c.2349C>T	p.Thr783Thr	synonymous_variant	Exon 21 of 43	1	NM_000037.4	ENSP00000289734.8		P16157-3

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32034

AN:

152136

Hom.:

4338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.259

AC:

65077

AN:

251288

Hom.:

9426

AF XY:

0.264

AC XY:

35925

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.0680

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.263

AC:

384291

AN:

1461628

Hom.:

52962

Cov.:

AF XY:

0.265

AC XY:

192933

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0464

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.0823

Gnomad4 SAS exome

AF:

0.314

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.210

AC:

32042

AN:

152254

Hom.:

4343

Cov.:

AF XY:

0.214

AC XY:

15946

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0548

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.0710

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.246

Hom.:

6204

Bravo

AF:

0.195

Asia WGS

AF:

0.221

AC:

769

AN:

3478

EpiCase

AF:

0.270

EpiControl

AF:

0.266

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spherocytosis type 1

Benign:5

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spherocytosis

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.4

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over