rs9855919

chr3-142515747-C-Achr3-142515747-C-T

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.4383-232G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,914 control chromosomes in the GnomAD database, including 31,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (31065 hom., cov: 30)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.423

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=-0.92).
• BP6: Variant 3-142515747-C-A is Benign according to our data. Variant chr3-142515747-C-A is described in ClinVar as [Benign]. Clinvar id is 678104.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
ATR	NM_001184.4	c.4383-232G>T		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.4383-232G>T		intron_variant		1	NM_001184.4	P1
ATR	ENST00000661310.1	c.4191-232G>T		intron_variant
ATR	ENST00000656590.1	c.3173-232G>T		intron_variant, NMD_transcript_variant
ATR	ENST00000653868.1	n.4412-232G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95601 AN: 151796 Hom.: 31018 Cov.: 30

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.630 AC: 95695 AN: 151914 Hom.: 31065 Cov.: 30 AF XY: 0.622 AC XY: 46175 AN XY: 74260

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.625

Alfa AF: 0.616 Hom.: 4111

Bravo AF: 0.636

Asia WGS AF: 0.505 AC: 1757 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	-0.92
Cadd	Benign	1.9
Dann	Benign	0.21

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: rs9855919; hg19: chr3-142234589;