rs6805118

Variant names:

• chr3-142498074-C-T
• rs6805118
• NM_001184.4:c.5558+523G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: Illumina, G2P, Ambry Genetics
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

  Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	NM_001184.4	MANE Select	c.5558+523G>A		intron	N/A	NP_001175.2
	ATR	NM_001354579.2		c.5366+523G>A		intron	N/A	NP_001341508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATR	ENST00000350721.9	TSL:1 MANE Select	c.5558+523G>A		intron	N/A	ENSP00000343741.4
	ATR	ENST00000513291.2	TSL:1	n.742+523G>A		intron	N/A
	ATR	ENST00000936442.1		c.5405+523G>A		intron	N/A	ENSP00000606501.1

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

African (AFR) AF: 0.0181 AC: 752 AN: 41534

American (AMR) AF: 0.0535 AC: 818 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5192

South Asian (SAS) AF: 0.100 AC: 483 AN: 4812

European-Finnish (FIN) AF: 0.102 AC: 1075 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6986 AN: 67968

Other (OTH) AF: 0.0658 AC: 139 AN: 2112

Alfa AF: 0.0917 Hom.: 937

Bravo AF: 0.0613

Asia WGS AF: 0.0480 AC: 169 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.54
PhyloP100		-0.30
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: rs6805118; hg19: chr3-142216916;