rs664982

Variant names:

• chr11-108354756-C-T
• rs664982
• NM_000051.4:c.8787-55C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-108354756-C-T
• chr11-108354756-C-A
• chr11-108354756-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.8787-55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,417,564 control chromosomes in the GnomAD database, including 227,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene ATM is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.54 (22541 hom., cov: 33)
  • Exomes 𝑓: 0.57 (204477 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.70
• Publications: 30 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]

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Specifications for ATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-108354756-C-T is Benign according to our data. Variant chr11-108354756-C-T is described in ClinVar as Benign. ClinVar VariationId is 1177616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 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.8787-55C>T		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.8787-55C>T		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.640+31164G>A		intron	N/A	NP_001317297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.8787-55C>T		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.8787-55C>T		intron	N/A	ENSP00000388058.2	Q13315
	C11orf65	ENST00000615746.4	TSL:1	c.*1196+159G>A		intron	N/A	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81656 AN: 151924 Hom.: 22528 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.566 AC: 716048 AN: 1265522 Hom.: 204477 AF XY: 0.570 AC XY: 365143 AN XY: 640216

African (AFR) AF: 0.412 AC: 12181 AN: 29540

American (AMR) AF: 0.636 AC: 28248 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 15305 AN: 24930

East Asian (EAS) AF: 0.459 AC: 17791 AN: 38762

South Asian (SAS) AF: 0.645 AC: 53026 AN: 82188

European-Finnish (FIN) AF: 0.626 AC: 33260 AN: 53102

Middle Eastern (MID) AF: 0.723 AC: 3898 AN: 5388

European-Non Finnish (NFE) AF: 0.559 AC: 521966 AN: 933178

Other (OTH) AF: 0.563 AC: 30373 AN: 53996

GnomAD4 genome AF: 0.537 AC: 81697 AN: 152042 Hom.: 22541 Cov.: 33 AF XY: 0.545 AC XY: 40516 AN XY: 74350

African (AFR) AF: 0.416 AC: 17225 AN: 41418

American (AMR) AF: 0.624 AC: 9531 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2218 AN: 3464

East Asian (EAS) AF: 0.436 AC: 2257 AN: 5180

South Asian (SAS) AF: 0.650 AC: 3141 AN: 4832

European-Finnish (FIN) AF: 0.630 AC: 6669 AN: 10578

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38651 AN: 67968

Other (OTH) AF: 0.569 AC: 1202 AN: 2112

Alfa AF: 0.413 Hom.: 1174

Bravo AF: 0.529

Asia WGS AF: 0.572 AC: 1990 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.65
PhyloP100		-1.7
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: rs664982; hg19: chr11-108225483; COSMIC: COSV53733871;