rs11927681

Variant names:

• chr3-142499506-G-T
• rs11927681
• NM_001184.4:c.5380+121C>A

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.5380+121C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 841,482 control chromosomes in the GnomAD database, including 3,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (539 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3048 hom.)
• Consequence: ATR NM_001184.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0940
• 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=-0.76).
• BP6: Variant 3-142499506-G-T is Benign according to our data. Variant chr3-142499506-G-T is described in ClinVar as Benign. ClinVar VariationId is 678211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 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.5380+121C>A		intron	N/A	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.5188+121C>A		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.5380+121C>A		intron	N/A	ENSP00000343741.4	Q13535-1
	ATR	ENST00000513291.2	TSL:1	n.564+121C>A		intron	N/A
	ATR	ENST00000936442.1		c.5227+121C>A		intron	N/A	ENSP00000606501.1

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10603 AN: 151994 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0206

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0964

GnomAD4 exome AF: 0.0848 AC: 58444 AN: 689370 Hom.: 3048 AF XY: 0.0839 AC XY: 30997 AN XY: 369478

African (AFR) AF: 0.0180 AC: 319 AN: 17676

American (AMR) AF: 0.0562 AC: 2251 AN: 40084

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2104 AN: 18592

East Asian (EAS) AF: 0.000296 AC: 9 AN: 30394

South Asian (SAS) AF: 0.0270 AC: 1900 AN: 70338

European-Finnish (FIN) AF: 0.0509 AC: 2261 AN: 44430

Middle Eastern (MID) AF: 0.123 AC: 484 AN: 3938

European-Non Finnish (NFE) AF: 0.108 AC: 46420 AN: 431630

Other (OTH) AF: 0.0835 AC: 2696 AN: 32288

GnomAD4 genome AF: 0.0697 AC: 10601 AN: 152112 Hom.: 539 Cov.: 32 AF XY: 0.0665 AC XY: 4945 AN XY: 74358

African (AFR) AF: 0.0184 AC: 763 AN: 41536

American (AMR) AF: 0.0697 AC: 1064 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3468

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4812

European-Finnish (FIN) AF: 0.0450 AC: 476 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7248 AN: 67976

Other (OTH) AF: 0.0950 AC: 200 AN: 2106

Alfa AF: 0.0830 Hom.: 88

Bravo AF: 0.0721

Asia WGS AF: 0.0140 AC: 48 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	-0.76
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		0.094
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: rs11927681; hg19: chr3-142218348;