rs9867946

chr3-142519150-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184.4(ATR):c.4382+519A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 152,188 control chromosomes in the GnomAD database, including 1,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (1087 hom., cov: 32)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4	c.4382+519A>C		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.4382+519A>C		intron_variant		1	NM_001184.4	P1
ATR	ENST00000661310.1	c.4190+519A>C		intron_variant
ATR	ENST00000656590.1	c.3172+519A>C		intron_variant, NMD_transcript_variant
ATR	ENST00000653868.1	n.4411+519A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0663 AC: 10089 AN: 152070 Hom.: 1079 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0466

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

GnomAD4 genome AF: 0.0665 AC: 10127 AN: 152188 Hom.: 1087 Cov.: 32 AF XY: 0.0645 AC XY: 4798 AN XY: 74420

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00868

Gnomad4 SAS AF: 0.0295

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0466

Alfa AF: 0.00908 Hom.: 172

Bravo AF: 0.0737

Asia WGS AF: 0.0350 AC: 120 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.4
Dann	Benign	0.66

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: rs9867946; hg19: chr3-142237992;