rs419716

Variant names:

• chr11-108350372-A-C
• rs419716
• NM_000051.4:c.8671+3007A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-108350372-A-C
• chr11-108350372-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.8671+3007A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,894 control chromosomes in the GnomAD database, including 21,832 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 0.53 (21832 hom., cov: 31)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 13 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=-0.96).
• 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+3007A>C		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+3007A>C		intron_variant	Intron 59 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79862 AN: 151776 Hom.: 21821 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.526 AC: 79896 AN: 151894 Hom.: 21832 Cov.: 31 AF XY: 0.535 AC XY: 39700 AN XY: 74246

African (AFR) AF: 0.378 AC: 15645 AN: 41430

American (AMR) AF: 0.617 AC: 9421 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2250 AN: 5164

South Asian (SAS) AF: 0.650 AC: 3126 AN: 4810

European-Finnish (FIN) AF: 0.629 AC: 6631 AN: 10536

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38619 AN: 67918

Other (OTH) AF: 0.562 AC: 1184 AN: 2108

Alfa AF: 0.475 Hom.: 2717

Bravo AF: 0.516

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-0.096
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: rs419716; hg19: chr11-108221099;