3-142498074-C-T

Position:

• chr3-142498074-C-T

Variant summary

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

The NM_001184.4(ATR):​c.5558+523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,174 control chromosomes in the GnomAD database, including 507 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 0.069 (507 hom., cov: 31)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATR	NM_001184.4	c.5558+523G>A		intron_variant		ENST00000350721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATR	ENST00000350721.9	c.5558+523G>A		intron_variant		1	NM_001184.4	P1

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10547 AN: 152056 Hom.: 503 Cov.: 31

Gnomad AFR AF: 0.0182

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0670

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

GnomAD4 genome AF: 0.0694 AC: 10555 AN: 152174 Hom.: 507 Cov.: 31 AF XY: 0.0676 AC XY: 5026 AN XY: 74404

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0720

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0918 Hom.: 723

Bravo AF: 0.0613

Asia WGS AF: 0.0480 AC: 169 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.54

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: rs6805118; hg19: chr3-142216916;