chr19-17283116-C-A

Position:

• chr19-17283116-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63

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]

ACMG classification

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/exons	MANE	UniProt
ANKLE1	NM_152363.6	c.461-109C>A		intron_variant		ENST00000404085.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKLE1	ENST00000404085.7	c.461-109C>A		intron_variant		2	NM_152363.6	P2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38364 AN: 151972 Hom.: 5179 Cov.: 32

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.: 35 AF XY: 0.268 AC XY: 183266 AN XY: 683158

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.: 32 AF XY: 0.248 AC XY: 18407 AN XY: 74364

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 27601076) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Other links and lift over

dbSNP: rs56069439; hg19: chr19-17393925;