chr3-142453938-T-C

Position:

• chr3-142453938-T-C

Variant summary

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

The NM_001184.4(ATR):​c.7656-705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,078 control chromosomes in the GnomAD database, including 30,328 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 0.62 (30328 hom., cov: 32)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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]

ATR (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATR	NM_001184.4	c.7656-705A>G		intron_variant		ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9	c.7656-705A>G		intron_variant		1	NM_001184.4	ENSP00000343741.4

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94428 AN: 151958 Hom.: 30284 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.622 AC: 94517 AN: 152078 Hom.: 30328 Cov.: 32 AF XY: 0.614 AC XY: 45634 AN XY: 74346

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.617

Alfa AF: 0.600 Hom.: 5239

Bravo AF: 0.628

Asia WGS AF: 0.505 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.41

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: rs9816736; hg19: chr3-142172780;