3-142515692-G-A

Position:

• chr3-142515692-G-A

Variant summary

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

The NM_001184.4(ATR):​c.4383-177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,976 control chromosomes in the GnomAD database, including 2,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2008 hom., cov: 31)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.664

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 3-142515692-G-A is Benign according to our data. Variant chr3-142515692-G-A is described in ClinVar as [Benign]. Clinvar id is 678203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4	c.4383-177C>T		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.4383-177C>T		intron_variant		1	NM_001184.4	P1
ATR	ENST00000661310.1	c.4191-177C>T		intron_variant
ATR	ENST00000656590.1	c.3173-177C>T		intron_variant, NMD_transcript_variant
ATR	ENST00000653868.1	n.4412-177C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22343 AN: 151858 Hom.: 2012 Cov.: 31

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0784

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22342 AN: 151976 Hom.: 2008 Cov.: 31 AF XY: 0.145 AC XY: 10740 AN XY: 74290

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.174

Alfa AF: 0.193 Hom.: 3999

Bravo AF: 0.141

Asia WGS AF: 0.105 AC: 362 AN: 3478

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

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	-0.85
CADD	Benign	6.0
DANN	Benign	0.53

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: rs10804682; hg19: chr3-142234534;