chr11-108236055-C-T

Position:

• chr11-108236055-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.496+221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 551,504 control chromosomes in the GnomAD database, including 104,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32708 hom., cov: 32)
  • Exomes 𝑓: 0.60 (71908 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.342

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-108236055-C-T is Benign according to our data. Variant chr11-108236055-C-T is described in ClinVar as [Benign]. Clinvar id is 1220661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4	c.496+221C>T		intron_variant		ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.496+221C>T		intron_variant			NM_000051.4	ENSP00000501606	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98536 AN: 151882 Hom.: 32657 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.597 AC: 238483 AN: 399502 Hom.: 71908 Cov.: 4 AF XY: 0.601 AC XY: 127821 AN XY: 212720

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.671

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.649

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.649 AC: 98639 AN: 152002 Hom.: 32708 Cov.: 32 AF XY: 0.653 AC XY: 48480 AN XY: 74264

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.656

Alfa AF: 0.601 Hom.: 12965

Bravo AF: 0.655

Asia WGS AF: 0.608 AC: 2115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.9
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs623860; hg19: chr11-108106782;