3-142503114-A-G

Position:

• chr3-142503114-A-G

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.5288+248T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,248 control chromosomes in the GnomAD database, including 65,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.92 (65034 hom., cov: 30)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-142503114-A-G is Benign according to our data. Variant chr3-142503114-A-G is described in ClinVar as [Benign]. Clinvar id is 678106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4	c.5288+248T>C		intron_variant		ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.5288+248T>C		intron_variant		1	NM_001184.4	ENSP00000343741.4

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140434 AN: 152130 Hom.: 64974 Cov.: 30

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.923 AC: 140554 AN: 152248 Hom.: 65034 Cov.: 30 AF XY: 0.922 AC XY: 68634 AN XY: 74418

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.917

Alfa AF: 0.897 Hom.: 13865

Bravo AF: 0.930

Asia WGS AF: 0.985 AC: 3425 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	-0.89
CADD	Benign	8.4
DANN	Benign	0.78

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: rs9856772; hg19: chr3-142221956;