chr11-108316229-T-C

Variant names:

• chr11-108316229-T-C
• rs4988084
• NM_000051.4:c.6198+116T>C

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.6198+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,037,554 control chromosomes in the GnomAD database, including 2,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (1359 hom., cov: 31)
  • Exomes 𝑓: 0.0092 (726 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.93
• Publications: 6 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=-0.91).
• BP6: Variant 11-108316229-T-C is Benign according to our data. Variant chr11-108316229-T-C is described in ClinVar as Benign. ClinVar VariationId is 675158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.6198+116T>C		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6198+116T>C		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-7158A>G		intron	N/A	NP_001317297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.6198+116T>C		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.6198+116T>C		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*1262+116T>C		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11096 AN: 152062 Hom.: 1354 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.0492

GnomAD4 exome AF: 0.00918 AC: 8132 AN: 885374 Hom.: 726 AF XY: 0.00773 AC XY: 3527 AN XY: 456490

African (AFR) AF: 0.248 AC: 5314 AN: 21438

American (AMR) AF: 0.0186 AC: 654 AN: 35146

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 311 AN: 22056

East Asian (EAS) AF: 0.000238 AC: 8 AN: 33586

South Asian (SAS) AF: 0.00184 AC: 127 AN: 69178

European-Finnish (FIN) AF: 0.0000437 AC: 2 AN: 45788

Middle Eastern (MID) AF: 0.0209 AC: 98 AN: 4698

European-Non Finnish (NFE) AF: 0.00117 AC: 716 AN: 612072

Other (OTH) AF: 0.0218 AC: 902 AN: 41412

GnomAD4 genome AF: 0.0731 AC: 11128 AN: 152180 Hom.: 1359 Cov.: 31 AF XY: 0.0696 AC XY: 5181 AN XY: 74416

African (AFR) AF: 0.249 AC: 10320 AN: 41460

American (AMR) AF: 0.0342 AC: 523 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00173 AC: 118 AN: 68020

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0658 Hom.: 118

Bravo AF: 0.0834

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.60
PhyloP100		-1.9
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: rs4988084; hg19: chr11-108186956;