rs227072

Variant names:

• chr11-108341366-A-C
• rs227072
• NM_000051.4:c.8269-1856A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-108341366-A-C
• chr11-108341366-A-G
• chr11-108341366-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.8269-1856A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,648 control chromosomes in the GnomAD database, including 22,634 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 0.54 (22634 hom., cov: 30)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 9 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=-0.92).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.8269-1856A>C		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.8269-1856A>C		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-32295T>G		intron	N/A	NP_001317297.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.8269-1856A>C		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.8269-1856A>C		intron	N/A	ENSP00000388058.2
	C11orf65	ENST00000615746.4	TSL:1	c.*1197-6074T>G		intron	N/A	ENSP00000483537.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81847 AN: 151530 Hom.: 22620 Cov.: 30

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.540 AC: 81890 AN: 151648 Hom.: 22634 Cov.: 30 AF XY: 0.548 AC XY: 40583 AN XY: 74100

African (AFR) AF: 0.425 AC: 17531 AN: 41270

American (AMR) AF: 0.624 AC: 9507 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2220 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2244 AN: 5154

South Asian (SAS) AF: 0.650 AC: 3124 AN: 4804

European-Finnish (FIN) AF: 0.631 AC: 6623 AN: 10502

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38633 AN: 67912

Other (OTH) AF: 0.571 AC: 1201 AN: 2104

Alfa AF: 0.413 Hom.: 1165

Bravo AF: 0.532

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.61
PhyloP100		-0.83
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: rs227072; hg19: chr11-108212093;