Variant 8-41661730-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000289734.13(ANK1):c.5544+146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,602,982 control chromosomes in the GnomAD database, including 474,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45020 hom., cov: 31)

Exomes 𝑓: 0.77 ( 428999 hom. )

Consequence

ANK1
ENST00000289734.13 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.142

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:

ANK1 (HGNC:):

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=-0.95).

BP6

Variant 8-41661730-T-C is Benign according to our data. Variant chr8-41661730-T-C is described in ClinVar as [Benign]. Clinvar id is 1262189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-41661730-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK1	NM_000037.4 linkuse as main transcript	c.5544+146A>G		intron_variant		ENST00000289734.13	NP_000028.3	P16157-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK1	ENST00000289734.13 linkuse as main transcript	c.5544+146A>G		intron_variant		1	NM_000037.4	ENSP00000289734.8		P16157-3

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

116821

AN:

151990

Hom.:

44969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.776

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.748

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.871

Gnomad SAS

AF:

0.803

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.749

GnomAD3 exomes

AF:

0.783

AC:

191940

AN:

245252

Hom.:

75455

AF XY:

0.781

AC XY:

103994

AN XY:

133162

show subpopulations

Gnomad AFR exome

AF:

0.774

Gnomad AMR exome

AF:

0.810

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.870

Gnomad SAS exome

AF:

0.804

Gnomad FIN exome

AF:

0.791

Gnomad NFE exome

AF:

0.761

Gnomad OTH exome

AF:

0.776

GnomAD4 exome

AF:

0.768

AC:

1114432

AN:

1450876

Hom.:

428999

Cov.:

AF XY:

0.768

AC XY:

554815

AN XY:

722458

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.863

Gnomad4 SAS exome

AF:

0.800

Gnomad4 FIN exome

AF:

0.795

Gnomad4 NFE exome

AF:

0.761

Gnomad4 OTH exome

AF:

0.772

GnomAD4 genome

AF:

0.769

AC:

116929

AN:

152106

Hom.:

45020

Cov.:

AF XY:

0.769

AC XY:

57190

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.777

Gnomad4 AMR

AF:

0.748

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.871

Gnomad4 SAS

AF:

0.802

Gnomad4 FIN

AF:

0.798

Gnomad4 NFE

AF:

0.760

Gnomad4 OTH

AF:

0.752

Alfa

AF:

0.756

Hom.:

82695

Bravo

AF:

0.764

Asia WGS

AF:

0.865

AC:

3010

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.19

DANN

Benign

0.37

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