Variant 19-17283116-C-A 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 NM_152363.6(ANKLE1):c.461-109C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,539,326 control chromosomes in the GnomAD database, including 58,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5182 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53602 hom. )

Consequence

ANKLE1
NM_152363.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.63

Variant links:

Genes affected

ANKLE1 (HGNC:26812): (ankyrin repeat and LEM domain containing 1) Enables endonuclease activity. Involved in positive regulation of response to DNA damage stimulus and protein export from nucleus. Located in cytosol and nucleoplasm. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKLE1 links:

ENSG00000269307 (HGNC:):

ENSG00000269307 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-17283116-C-A is Benign according to our data. Variant chr19-17283116-C-A is described in ClinVar as [Benign]. Clinvar id is 1281673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE1	NM_152363.6 link	c.461-109C>A		intron_variant	Intron 4 of 8	ENST00000404085.7	NP_689576.6	Q8NAG6-2A0A499FJM0B4E124

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE1	ENST00000404085.7 link	c.461-109C>A		intron_variant	Intron 4 of 8	2	NM_152363.6	ENSP00000384008.3		Q8NAG6-2
ENSG00000269307	ENST00000596542.1 link	n.*907C>A		downstream_gene_variant		2		ENSP00000469159.2		M0QXG9

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38364

AN:

151972

Hom.:

5179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.250

GnomAD4 exome

AF:

0.270

AC:

375205

AN:

1387236

Hom.:

53602

Cov.:

AF XY:

0.268

AC XY:

183266

AN XY:

683158

show subpopulations

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.252

AC:

38374

AN:

152090

Hom.:

5182

Cov.:

AF XY:

0.248

AC XY:

18407

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.286

Hom.:

1484

Bravo

AF:

0.240

Asia WGS

AF:

0.0870

AC:

303

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

Jan 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27601076) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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