rs371454519

chr19-17286684-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152363.6(ANKLE1):c.*132G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,012,124 control chromosomes in the GnomAD database, including 1,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (565 hom., cov: 26)
  • Exomes 𝑓: 0.13 (893 hom.)
• Consequence: ANKLE1 NM_152363.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.223

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-17286684-G-T is Benign according to our data. Variant chr19-17286684-G-T is described in ClinVar as [Benign]. Clinvar id is 402368.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKLE1	NM_152363.6	c.*132G>T		3_prime_UTR_variant	9/9	ENST00000404085.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKLE1	ENST00000404085.7	c.*132G>T		3_prime_UTR_variant	9/9	2	NM_152363.6	P2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 11660 AN: 114518 Hom.: 562 Cov.: 26

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00206

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.0805 AC: 5869 AN: 72870 Hom.: 119 AF XY: 0.0801 AC XY: 3057 AN XY: 38158

Gnomad AFR exome AF: 0.0519

Gnomad AMR exome AF: 0.0600

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.00147

Gnomad SAS exome AF: 0.0463

Gnomad FIN exome AF: 0.0888

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.129 AC: 116096 AN: 897520 Hom.: 893 Cov.: 28 AF XY: 0.128 AC XY: 55880 AN XY: 438002

Gnomad4 AFR exome AF: 0.0628

Gnomad4 AMR exome AF: 0.0640

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.00150

Gnomad4 SAS exome AF: 0.0520

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.102 AC: 11667 AN: 114604 Hom.: 565 Cov.: 26 AF XY: 0.0987 AC XY: 5505 AN XY: 55762

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.0897

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00206

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.0963

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0819 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside ROI, Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.76

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: rs371454519; hg19: chr19-17397493; COSMIC: COSV66731792; COSMIC: COSV66731792;