rs11920625

chr3-142542497-G-Achr3-142542497-G-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.3450+168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,146 control chromosomes in the GnomAD database, including 414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (414 hom., cov: 32)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500

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=-0.86).
• BP6: Variant 3-142542497-G-A is Benign according to our data. Variant chr3-142542497-G-A is described in ClinVar as [Benign]. Clinvar id is 1257267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4	c.3450+168C>T		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.3450+168C>T		intron_variant		1	NM_001184.4	P1

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9440 AN: 152028 Hom.: 414 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0891

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0620 AC: 9438 AN: 152146 Hom.: 414 Cov.: 32 AF XY: 0.0596 AC XY: 4430 AN XY: 74346

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0891

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.0959

Gnomad4 OTH AF: 0.0800

Alfa AF: 0.0395 Hom.: 52

Bravo AF: 0.0635

Asia WGS AF: 0.0190 AC: 67 AN: 3476

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

Jul 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.23
Dann	Benign	0.44

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: rs11920625; hg19: chr3-142261339;