3-142449134-A-G

Position:

• chr3-142449134-A-G

Variant summary

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

The ENST00000658083.1(ATR):​n.3410T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 337,736 control chromosomes in the GnomAD database, including 21,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8985 hom., cov: 33)
  • Exomes 𝑓: 0.36 (12359 hom.)
• Consequence: ATR ENST00000658083.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349

Genes affected

ATR (HGNC:882): (ATR serine/threonine kinase) The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-142449134-A-G is Benign according to our data. Variant chr3-142449134-A-G is described in ClinVar as [Benign]. Clinvar id is 1270471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000658083.1	n.3410T>C		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50917 AN: 151982 Hom.: 8981 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.357 AC: 66245 AN: 185636 Hom.: 12359 AF XY: 0.354 AC XY: 34345 AN XY: 97150

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.335 AC: 50939 AN: 152100 Hom.: 8985 Cov.: 33 AF XY: 0.335 AC XY: 24912 AN XY: 74334

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.365

Alfa AF: 0.369 Hom.: 3333

Bravo AF: 0.330

Asia WGS AF: 0.324 AC: 1124 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10935463; hg19: chr3-142167976;