rs9855919

Variant names:

• chr3-142515747-C-A
• rs9855919
• NM_001184.4:c.4383-232G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-142515747-C-A
• chr3-142515747-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001184.4(ATR):​c.4383-232G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,914 control chromosomes in the GnomAD database, including 31,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (31065 hom., cov: 30)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.423
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Seckel syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Illumina
• familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• familial prostate carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-142515747-C-A is Benign according to our data. Variant chr3-142515747-C-A is described in ClinVar as Benign. ClinVar VariationId is 678104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	NM_001184.4	MANE Select	c.4383-232G>T		intron	N/A	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.4191-232G>T		intron	N/A	NP_001341508.1	Q13535-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	ENST00000350721.9	TSL:1 MANE Select	c.4383-232G>T		intron	N/A	ENSP00000343741.4	Q13535-1
	ATR	ENST00000936442.1		c.4230-232G>T		intron	N/A	ENSP00000606501.1
	ATR	ENST00000661310.1		c.4191-232G>T		intron	N/A	ENSP00000499589.1	Q13535-2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95601 AN: 151796 Hom.: 31018 Cov.: 30

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.630 AC: 95695 AN: 151914 Hom.: 31065 Cov.: 30 AF XY: 0.622 AC XY: 46175 AN XY: 74260

African (AFR) AF: 0.793 AC: 32870 AN: 41442

American (AMR) AF: 0.533 AC: 8142 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1972 AN: 3466

East Asian (EAS) AF: 0.466 AC: 2401 AN: 5154

South Asian (SAS) AF: 0.443 AC: 2132 AN: 4812

European-Finnish (FIN) AF: 0.548 AC: 5779 AN: 10550

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40266 AN: 67902

Other (OTH) AF: 0.625 AC: 1318 AN: 2108

Alfa AF: 0.623 Hom.: 4370

Bravo AF: 0.636

Asia WGS AF: 0.505 AC: 1757 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.21
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9855919; hg19: chr3-142234589;