11-108344670-T-G

Variant names:

• chr11-108344670-T-G
• rs17503908
• NM_000051.4:c.8419-1073T>G

Variant summary

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

The NM_000051.4(ATM):​c.8419-1073T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 151,960 control chromosomes in the GnomAD database, including 445 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 0.067 (445 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.8419-1073T>G		intron_variant	Intron 57 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.8419-1073T>G		intron_variant	Intron 57 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10196 AN: 151842 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0671 AC: 10199 AN: 151960 Hom.: 445 Cov.: 32 AF XY: 0.0651 AC XY: 4836 AN XY: 74250

African (AFR) AF: 0.0176 AC: 730 AN: 41472

American (AMR) AF: 0.0948 AC: 1445 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3466

East Asian (EAS) AF: 0.0409 AC: 211 AN: 5162

South Asian (SAS) AF: 0.0339 AC: 163 AN: 4804

European-Finnish (FIN) AF: 0.0531 AC: 561 AN: 10556

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6422 AN: 67948

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0780 Hom.: 163

Bravo AF: 0.0688

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.62
PhyloP100		0.0080
Mutation Taster		=99/1	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: rs17503908; hg19: chr11-108215397;