3-48446788-G-C

Position:

• chr3-48446788-G-C

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.-58G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,354,010 control chromosomes in the GnomAD database, including 24,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1970 hom., cov: 32)
  • Exomes 𝑓: 0.19 (22834 hom.)
• Consequence: ATRIP NM_130384.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.171

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=-0.8).
• BP6: Variant 3-48446788-G-C is Benign according to our data. Variant chr3-48446788-G-C is described in ClinVar as [Benign]. Clinvar id is 1230187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRIP	NM_130384.3	c.-58G>C		5_prime_UTR_variant	1/13	ENST00000320211.10
ATRIP-TREX1	NR_153405.1	n.10G>C		non_coding_transcript_exon_variant	1/15
ATRIP	NM_001271022.2	c.-229G>C		5_prime_UTR_variant	1/14
ATRIP	NM_032166.4	c.-58G>C		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRIP	ENST00000320211.10	c.-58G>C		5_prime_UTR_variant	1/13	1	NM_130384.3	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22442 AN: 152044 Hom.: 1967 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.191 AC: 229381 AN: 1201852 Hom.: 22834 Cov.: 31 AF XY: 0.191 AC XY: 111353 AN XY: 581640

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.0472

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.148 AC: 22451 AN: 152158 Hom.: 1970 Cov.: 32 AF XY: 0.147 AC XY: 10903 AN XY: 74376

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0627 Hom.: 85

Bravo AF: 0.144

Asia WGS AF: 0.142 AC: 494 AN: 3470

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	Jul 09, 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	-0.80
CADD	Benign	6.5
DANN	Benign	0.60

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: rs72622933; hg19: chr3-48488192;