rs9869842

Positions:

• chr3-142553472-G-A

Variant summary

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

The NM_001184.4(ATR):​c.2634-74C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,502,864 control chromosomes in the GnomAD database, including 253,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30711 hom., cov: 31)
  • Exomes 𝑓: 0.57 (223274 hom.)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79

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]

ATR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 3-142553472-G-A is Benign according to our data. Variant chr3-142553472-G-A is described in ClinVar as [Benign]. Clinvar id is 670440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4	c.2634-74C>T		intron_variant		ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.2634-74C>T		intron_variant		1	NM_001184.4	ENSP00000343741.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 94929 AN: 151498 Hom.: 30660 Cov.: 31

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.621

GnomAD4 exome AF: 0.572 AC: 772814 AN: 1351248 Hom.: 223274 Cov.: 24 AF XY: 0.568 AC XY: 384269 AN XY: 676562

Gnomad4 AFR exome AF: 0.800

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.627 AC: 95027 AN: 151616 Hom.: 30711 Cov.: 31 AF XY: 0.619 AC XY: 45855 AN XY: 74086

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.626

Alfa AF: 0.618 Hom.: 4322

Bravo AF: 0.633

Asia WGS AF: 0.506 AC: 1760 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.081
DANN	Benign	0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9869842; hg19: chr3-142272314; COSMIC: COSV63385113; COSMIC: COSV63385113;