NM_000051.4:c.7630-17T>C

Variant names:

• chr11-108331862-T-C
• rs116047570
• NM_000051.4:c.7630-17T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000051.4(ATM):​c.7630-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,611,998 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (3 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.253
• Publications: 2 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=-0.65).
• BP6: Variant 11-108331862-T-C is Benign according to our data. Variant chr11-108331862-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00254 (387/152332) while in subpopulation AFR AF = 0.00868 (361/41580). AF 95% confidence interval is 0.00794. There are 1 homozygotes in GnomAd4. There are 179 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

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.7630-17T>C		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.7630-17T>C		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-22791A>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.7630-17T>C		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.7630-17T>C		intron	N/A	ENSP00000388058.2
	C11orf65	ENST00000615746.4	TSL:1	c.*1270-295A>G		intron	N/A	ENSP00000483537.1

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 383 AN: 152214 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000765 AC: 192 AN: 250882 AF XY: 0.000626

Gnomad AFR exome AF: 0.00873

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000235 AC: 343 AN: 1459666 Hom.: 3 Cov.: 31 AF XY: 0.000200 AC XY: 145 AN XY: 726256

African (AFR) AF: 0.00688 AC: 230 AN: 33408

American (AMR) AF: 0.00119 AC: 53 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1110210

Other (OTH) AF: 0.000779 AC: 47 AN: 60314

GnomAD4 genome AF: 0.00254 AC: 387 AN: 152332 Hom.: 1 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74494

African (AFR) AF: 0.00868 AC: 361 AN: 41580

American (AMR) AF: 0.00111 AC: 17 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00241

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	2	Familial cancer of breast (2)
-	-	2	not specified (2)
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Breast and/or ovarian cancer (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

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: rs116047570; hg19: chr11-108202589;