rs56013141

Positions:

• chr11-108287478-TC-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000051.4(ATM):​c.3994-121del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 603,396 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.556

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 -16 ACMG points.

• BP6: Variant 11-108287478-TC-T is Benign according to our data. Variant chr11-108287478-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 254751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108287478-TC-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00586 (892/152268) while in subpopulation AFR AF= 0.0174 (724/41550). AF 95% confidence interval is 0.0164. There are 9 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4	c.3994-121del		intron_variant		ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.3994-121del		intron_variant			NM_000051.4	ENSP00000501606	P1

Frequencies

GnomAD3 genomes AF: 0.00587 AC: 893 AN: 152150 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.00155 AC: 699 AN: 451128 Hom.: 2 Cov.: 6 AF XY: 0.00152 AC XY: 365 AN XY: 240796

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.00230

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00134

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000427

Gnomad4 OTH exome AF: 0.00291

GnomAD4 genome AF: 0.00586 AC: 892 AN: 152268 Hom.: 9 Cov.: 32 AF XY: 0.00551 AC XY: 410 AN XY: 74462

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00484 Hom.: 0

Bravo AF: 0.00715

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Ataxia-telangiectasia syndrome Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 25, 2019

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs56013141; hg19: chr11-108158205;