rs170548

Variant names:

• chr11-108364109-A-C
• rs170548
• NM_000051.4:c.8851-973A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-108364109-A-C
• chr11-108364109-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.8851-973A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,964 control chromosomes in the GnomAD database, including 7,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.28 (7235 hom., cov: 31)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-108364109-A-C is Benign according to our data. Variant chr11-108364109-A-C is described in ClinVar as Benign. ClinVar VariationId is 489601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.8851-973A>C		intron_variant	Intron 61 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.8851-973A>C		intron_variant	Intron 61 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42861 AN: 151846 Hom.: 7236 Cov.: 31

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.282 AC: 42860 AN: 151964 Hom.: 7235 Cov.: 31 AF XY: 0.292 AC XY: 21665 AN XY: 74288

African (AFR) AF: 0.0991 AC: 4112 AN: 41500

American (AMR) AF: 0.408 AC: 6223 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1850 AN: 5160

South Asian (SAS) AF: 0.495 AC: 2384 AN: 4816

European-Finnish (FIN) AF: 0.338 AC: 3552 AN: 10520

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22331 AN: 67920

Other (OTH) AF: 0.330 AC: 698 AN: 2112

Alfa AF: 0.195 Hom.: 711

Bravo AF: 0.276

Asia WGS AF: 0.445 AC: 1545 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ataxia-telangiectasia syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Nov 26, 2014

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.30
PhyloP100		1.0
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: rs170548; hg19: chr11-108234836;