rs425061

Variant names:

• chr11-108348693-G-A
• rs425061
• NM_000051.4:c.8671+1328G>A

Variant summary

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

The NM_000051.4(ATM):​c.8671+1328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,700 control chromosomes in the GnomAD database, including 21,694 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 0.52 (21694 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• Publications: 5 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.8671+1328G>A		intron_variant	Intron 59 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.8671+1328G>A		intron_variant	Intron 59 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79458 AN: 151580 Hom.: 21682 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.524 AC: 79494 AN: 151700 Hom.: 21694 Cov.: 32 AF XY: 0.533 AC XY: 39512 AN XY: 74128

African (AFR) AF: 0.371 AC: 15362 AN: 41392

American (AMR) AF: 0.617 AC: 9414 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2221 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2239 AN: 5142

South Asian (SAS) AF: 0.650 AC: 3128 AN: 4814

European-Finnish (FIN) AF: 0.631 AC: 6623 AN: 10488

Middle Eastern (MID) AF: 0.719 AC: 197 AN: 274

European-Non Finnish (NFE) AF: 0.568 AC: 38550 AN: 67852

Other (OTH) AF: 0.560 AC: 1173 AN: 2096

Alfa AF: 0.534 Hom.: 2867

Bravo AF: 0.513

Asia WGS AF: 0.566 AC: 1939 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.72
DANN	Benign	0.58
PhyloP100		-0.86
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: rs425061; hg19: chr11-108219420;