3-48446745-C-G

Variant names:

• chr3-48446745-C-G
• rs116253015
• NM_130384.3:c.-101C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130384.3(ATRIP):​c.-101C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,304,516 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (38 hom.)
• Consequence: ATRIP NM_130384.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

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]

CCDC51 (HGNC:25714): (coiled-coil domain containing 51) Enables mitochondrial ATP-gated potassium channel activity. Involved in potassium ion transmembrane transport. Is integral component of mitochondrial inner membrane. Part of mitochondrial ATP-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000244380 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-48446745-C-G is Benign according to our data. Variant chr3-48446745-C-G is described in ClinVar as Benign. ClinVar VariationId is 1262894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130384.3. 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
	ATRIP	NM_130384.3	MANE Select	c.-101C>G		5_prime_UTR	Exon 1 of 13	NP_569055.1	Q8WXE1-1
	ATRIP	NM_032166.4		c.-101C>G		5_prime_UTR	Exon 1 of 12	NP_115542.2
	ATRIP	NM_001271022.2		c.-272C>G		5_prime_UTR	Exon 1 of 14	NP_001257951.1	Q8WXE1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.-101C>G		5_prime_UTR	Exon 1 of 13	ENSP00000323099.3	Q8WXE1-1
	ATRIP	ENST00000346691.9	TSL:1	c.-101C>G		5_prime_UTR	Exon 1 of 12	ENSP00000302338.5	Q8WXE1-2
	ATRIP	ENST00000949799.1		c.-101C>G		5_prime_UTR	Exon 1 of 14	ENSP00000619858.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2570 AN: 152030 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00232 AC: 2673 AN: 1152374 Hom.: 38 Cov.: 24 AF XY: 0.00225 AC XY: 1248 AN XY: 554224

African (AFR) AF: 0.0571 AC: 1371 AN: 24018

American (AMR) AF: 0.00512 AC: 83 AN: 16214

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 253 AN: 14950

East Asian (EAS) AF: 0.00 AC: 0 AN: 29150

South Asian (SAS) AF: 0.000125 AC: 4 AN: 31936

European-Finnish (FIN) AF: 0.0000599 AC: 2 AN: 33408

Middle Eastern (MID) AF: 0.0103 AC: 31 AN: 2998

European-Non Finnish (NFE) AF: 0.000671 AC: 640 AN: 953662

Other (OTH) AF: 0.00628 AC: 289 AN: 46038

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152142 Hom.: 62 Cov.: 33 AF XY: 0.0169 AC XY: 1257 AN XY: 74368

African (AFR) AF: 0.0549 AC: 2279 AN: 41526

American (AMR) AF: 0.00902 AC: 138 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 67948

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0132 Hom.: 5

Bravo AF: 0.0193

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		0.63
PromoterAI		0.0011	Neutral
Mutation Taster		=299/1	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: rs116253015; hg19: chr3-48488149;