rs11927681

Variant names:

• chr3-142499506-G-T
• rs11927681
• NM_001184.4:c.5380+121C>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.5380+121C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 841,482 control chromosomes in the GnomAD database, including 3,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (539 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3048 hom.)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0940

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=-0.76).
• BP6: Variant 3-142499506-G-T is Benign according to our data. Variant chr3-142499506-G-T is described in ClinVar as [Benign]. Clinvar id is 678211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATR	NM_001184.4	c.5380+121C>A		intron_variant	Intron 31 of 46	ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.5380+121C>A		intron_variant	Intron 31 of 46	1	NM_001184.4	ENSP00000343741.4

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10603 AN: 151994 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0206

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0964

GnomAD4 exome AF: 0.0848 AC: 58444 AN: 689370 Hom.: 3048 AF XY: 0.0839 AC XY: 30997 AN XY: 369478

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.0562

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.000296

Gnomad4 SAS exome AF: 0.0270

Gnomad4 FIN exome AF: 0.0509

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0835

GnomAD4 genome AF: 0.0697 AC: 10601 AN: 152112 Hom.: 539 Cov.: 32 AF XY: 0.0665 AC XY: 4945 AN XY: 74358

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0950

Alfa AF: 0.0830 Hom.: 88

Bravo AF: 0.0721

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.76
CADD	Benign	11
DANN	Benign	0.95

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: rs11927681; hg19: chr3-142218348;