rs1799757

Variant names:

• chr11-108279480-CT-C
• rs1799757
• NM_000051.4:c.3285-9delT

Your query was ambiguous. Multiple possible variants found:

• chr11-108279480-CT-C
• chr11-108279480-CT-CTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.3285-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,573,082 control chromosomes in the GnomAD database, including 14,912 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1202 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13710 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:20
• Conservation: PhyloP100: 0.508
• Publications: 19 publications found

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ATM Gene-Disease associations (from GenCC):

• ATM-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• ataxia telangiectasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
• prostate cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• gastric carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-108279480-CT-C is Benign according to our data. Variant chr11-108279480-CT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 181857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. 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
	ATM	NM_000051.4	MANE Select	c.3285-9delT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3285-9delT		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.3285-10delT		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.3285-10delT		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000531525.3	TSL:1	c.3285-10delT		intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16172 AN: 152030 Hom.: 1202 Cov.: 31

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00788

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.113 AC: 25710 AN: 227570 AF XY: 0.115

Gnomad AFR exome AF: 0.0227

Gnomad AMR exome AF: 0.0614

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.00632

Gnomad FIN exome AF: 0.241

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.132 AC: 187000 AN: 1420934 Hom.: 13710 Cov.: 21 AF XY: 0.131 AC XY: 92695 AN XY: 707534

African (AFR) AF: 0.0209 AC: 682 AN: 32554

American (AMR) AF: 0.0646 AC: 2745 AN: 42482

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3437 AN: 25698

East Asian (EAS) AF: 0.00314 AC: 123 AN: 39140

South Asian (SAS) AF: 0.0772 AC: 6505 AN: 84220

European-Finnish (FIN) AF: 0.235 AC: 12359 AN: 52672

Middle Eastern (MID) AF: 0.119 AC: 677 AN: 5696

European-Non Finnish (NFE) AF: 0.142 AC: 153389 AN: 1079588

Other (OTH) AF: 0.120 AC: 7083 AN: 58884

GnomAD4 genome AF: 0.106 AC: 16175 AN: 152148 Hom.: 1202 Cov.: 31 AF XY: 0.108 AC XY: 8065 AN XY: 74370

African (AFR) AF: 0.0239 AC: 995 AN: 41560

American (AMR) AF: 0.0916 AC: 1400 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3470

East Asian (EAS) AF: 0.00790 AC: 41 AN: 5188

South Asian (SAS) AF: 0.0762 AC: 367 AN: 4816

European-Finnish (FIN) AF: 0.237 AC: 2512 AN: 10578

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9821 AN: 67950

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.125 Hom.: 256

Bravo AF: 0.0928

Asia WGS AF: 0.0370 AC: 128 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	9	not specified (9)
-	-	4	Ataxia-telangiectasia syndrome (4)
-	-	3	not provided (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	Familial cancer of breast (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
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: rs1799757; hg19: chr11-108150207;