rs3135936

chr3-48464819-C-A

Variant summary

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

The NM_130384.3(ATRIP):c.2056-12C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,604,518 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (276 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (273 hom.)
• Consequence: ATRIP NM_130384.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004487
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.214

Genes affected

ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ATRIP-TREX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-48464819-C-A is Benign according to our data. Variant chr3-48464819-C-A is described in ClinVar as [Benign]. Clinvar id is 1276028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRIP	NM_130384.3	c.2056-12C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000320211.10
ATRIP-TREX1	NR_153405.1	n.2208-12C>A		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRIP	ENST00000320211.10	c.2056-12C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_130384.3	P1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5225 AN: 152108 Hom.: 268 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0101 AC: 2504 AN: 247566 Hom.: 109 AF XY: 0.00765 AC XY: 1024 AN XY: 133836

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00802

Gnomad ASJ exome AF: 0.0192

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00131

Gnomad OTH exome AF: 0.00811

GnomAD4 exome AF: 0.00459 AC: 6664 AN: 1452292 Hom.: 273 Cov.: 35 AF XY: 0.00421 AC XY: 3034 AN XY: 720554

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00890

Gnomad4 ASJ exome AF: 0.0170

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000291

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.000925

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0346 AC: 5267 AN: 152226 Hom.: 276 Cov.: 33 AF XY: 0.0343 AC XY: 2556 AN XY: 74432

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0175 Hom.: 24

Bravo AF: 0.0396

Asia WGS AF: 0.00808 AC: 28 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	Oct 06, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.5
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.050		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: rs3135936; hg19: chr3-48506218;