rs11916455

chr3-142503232-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.5288+130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 632,804 control chromosomes in the GnomAD database, including 44,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9410 hom., cov: 32)
  • Exomes 𝑓: 0.37 (34739 hom.)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.961

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 3-142503232-C-T is Benign according to our data. Variant chr3-142503232-C-T is described in ClinVar as [Benign]. Clinvar id is 678204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4	c.5288+130G>A		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.5288+130G>A		intron_variant		1	NM_001184.4	P1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51940 AN: 151892 Hom.: 9406 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.371 AC: 178374 AN: 480794 Hom.: 34739 AF XY: 0.368 AC XY: 93847 AN XY: 255316

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.398

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.342 AC: 51962 AN: 152010 Hom.: 9410 Cov.: 32 AF XY: 0.342 AC XY: 25400 AN XY: 74328

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.372

Alfa AF: 0.375 Hom.: 1417

Bravo AF: 0.337

Asia WGS AF: 0.323 AC: 1122 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	7.3
Dann	Benign	0.55

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: rs11916455; hg19: chr3-142222074;