rs611018

Variant names:

• chr11-108315222-A-G
• rs611018
• NM_000051.4:c.6007-601A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-108315222-A-G
• chr11-108315222-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000051.4(ATM):​c.6007-601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,328 control chromosomes in the GnomAD database, including 68,251 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 0.95 (68251 hom., cov: 33)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 7 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.6007-601A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6007-601A>G		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-6151T>C		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.6007-601A>G		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.6007-601A>G		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*1071-601A>G		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143971 AN: 152210 Hom.: 68191 Cov.: 33

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.943

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.946 AC: 144090 AN: 152328 Hom.: 68251 Cov.: 33 AF XY: 0.948 AC XY: 70568 AN XY: 74476

African (AFR) AF: 0.985 AC: 40963 AN: 41570

American (AMR) AF: 0.942 AC: 14417 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3208 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5180 AN: 5192

South Asian (SAS) AF: 0.955 AC: 4607 AN: 4826

European-Finnish (FIN) AF: 0.941 AC: 9992 AN: 10618

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62644 AN: 68034

Other (OTH) AF: 0.944 AC: 1993 AN: 2112

Alfa AF: 0.932 Hom.: 8499

Bravo AF: 0.947

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.063
DANN	Benign	0.25
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs611018; hg19: chr11-108185949;