rs56013141

Variant names:

• chr11-108287478-TC-T
• rs56013141
• NM_000051.4:c.3994-121delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000051.4(ATM):​c.3994-121delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 603,396 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.556
• Publications: 2 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 11-108287478-TC-T is Benign according to our data. Variant chr11-108287478-TC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 254751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00586 (892/152268) while in subpopulation AFR AF = 0.0174 (724/41550). AF 95% confidence interval is 0.0164. There are 9 homozygotes in GnomAd4. There are 410 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AD,AR gene

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.3994-121delC		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3994-121delC		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.3994-121delC		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.3994-121delC		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000531525.3	TSL:1	c.3994-121delC		intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes AF: 0.00587 AC: 893 AN: 152150 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00155 AC: 699 AN: 451128 Hom.: 2 Cov.: 6 AF XY: 0.00152 AC XY: 365 AN XY: 240796

African (AFR) AF: 0.0170 AC: 204 AN: 12014

American (AMR) AF: 0.00230 AC: 42 AN: 18240

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 208 AN: 14322

East Asian (EAS) AF: 0.00 AC: 0 AN: 29214

South Asian (SAS) AF: 0.00134 AC: 47 AN: 35094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26684

Middle Eastern (MID) AF: 0.000507 AC: 1 AN: 1974

European-Non Finnish (NFE) AF: 0.000427 AC: 123 AN: 288176

Other (OTH) AF: 0.00291 AC: 74 AN: 25410

GnomAD4 genome AF: 0.00586 AC: 892 AN: 152268 Hom.: 9 Cov.: 32 AF XY: 0.00551 AC XY: 410 AN XY: 74462

African (AFR) AF: 0.0174 AC: 724 AN: 41550

American (AMR) AF: 0.00504 AC: 77 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68020

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00484 Hom.: 0

Bravo AF: 0.00715

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

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: rs56013141; hg19: chr11-108158205;