rs6782400

Positions:

• chr3-142576526-C-A

Variant summary

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

The NM_001184.4(ATR):​c.59+2120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,012 control chromosomes in the GnomAD database, including 31,122 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 0.63 (31122 hom., cov: 32)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4	c.59+2120G>T		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.59+2120G>T		intron_variant		1	NM_001184.4	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95547 AN: 151894 Hom.: 31069 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.629 AC: 95647 AN: 152012 Hom.: 31122 Cov.: 32 AF XY: 0.622 AC XY: 46186 AN XY: 74300

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.629

Alfa AF: 0.620 Hom.: 4357

Bravo AF: 0.636

Asia WGS AF: 0.509 AC: 1769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.4
DANN	Benign	0.63

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: rs6782400; hg19: chr3-142295368;