rs371454519

Variant names:

• chr19-17286684-G-T
• rs371454519
• NM_152363.6:c.*132G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.223
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.041).
• BP6: Variant 19-17286684-G-T is Benign according to our data. Variant chr19-17286684-G-T is described in ClinVar as Benign. ClinVar VariationId is 402368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE1	NM_152363.6	c.*132G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000404085.7	NP_689576.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE1	ENST00000404085.7	c.*132G>T		3_prime_UTR_variant	Exon 9 of 9	2	NM_152363.6	ENSP00000384008.3

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

GnomAD2 exomes AF: 0.0805 AC: 5869 AN: 72870 AF XY: 0.0801

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 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

African (AFR) AF: 0.0628 AC: 1149 AN: 18288

American (AMR) AF: 0.0640 AC: 1547 AN: 24186

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 2149 AN: 14152

East Asian (EAS) AF: 0.00150 AC: 41 AN: 27368

South Asian (SAS) AF: 0.0520 AC: 2502 AN: 48136

European-Finnish (FIN) AF: 0.124 AC: 2259 AN: 18164

Middle Eastern (MID) AF: 0.121 AC: 427 AN: 3528

European-Non Finnish (NFE) AF: 0.144 AC: 101702 AN: 706436

Other (OTH) AF: 0.116 AC: 4320 AN: 37262

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

African (AFR) AF: 0.0693 AC: 1678 AN: 24206

American (AMR) AF: 0.0897 AC: 1080 AN: 12044

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 369 AN: 2916

East Asian (EAS) AF: 0.00206 AC: 9 AN: 4368

South Asian (SAS) AF: 0.0396 AC: 158 AN: 3992

European-Finnish (FIN) AF: 0.0963 AC: 768 AN: 7972

Middle Eastern (MID) AF: 0.0969 AC: 25 AN: 258

European-Non Finnish (NFE) AF: 0.129 AC: 7282 AN: 56374

Other (OTH) AF: 0.117 AC: 191 AN: 1630

Alfa AF: 0.0819 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

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	-0.83
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.22
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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