rs227062

Variant names:

• chr11-108334656-G-A
• rs227062
• NM_000051.4:c.8011-313G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000051.4(ATM):​c.8011-313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,994 control chromosomes in the GnomAD database, including 22,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (22587 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.62
• Publications: 17 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-108334656-G-A is Benign according to our data. Variant chr11-108334656-G-A is described in ClinVar as Benign. ClinVar VariationId is 1252182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 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.8011-313G>A		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.8011-313G>A		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-25585C>T		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.8011-313G>A		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.8011-313G>A		intron	N/A	ENSP00000388058.2	Q13315
	C11orf65	ENST00000615746.4	TSL:1	c.*1269+564C>T		intron	N/A	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81752 AN: 151876 Hom.: 22574 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.750

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: 0.538 AC: 81793 AN: 151994 Hom.: 22587 Cov.: 32 AF XY: 0.546 AC XY: 40543 AN XY: 74278

African (AFR) AF: 0.419 AC: 17361 AN: 41454

American (AMR) AF: 0.623 AC: 9528 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2220 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2245 AN: 5158

South Asian (SAS) AF: 0.650 AC: 3138 AN: 4824

European-Finnish (FIN) AF: 0.631 AC: 6643 AN: 10526

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38648 AN: 67960

Other (OTH) AF: 0.571 AC: 1204 AN: 2110

Alfa AF: 0.541 Hom.: 3396

Bravo AF: 0.529

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.53
PhyloP100		-1.6
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: rs227062; hg19: chr11-108205383;