7-105542599-C-T

Variant names:

• chr7-105542599-C-T
• rs79893877
• NM_021930.6:c.465C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001346601.2(RINT1):​c.-458C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,613,976 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (16 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (112 hom.)
• Consequence: RINT1 NM_001346601.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.370

Genes affected

RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-105542599-C-T is Benign according to our data. Variant chr7-105542599-C-T is described in ClinVar as [Benign]. Clinvar id is 416394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0063 (959/152202) while in subpopulation EAS AF= 0.0353 (183/5186). AF 95% confidence interval is 0.0311. There are 16 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RINT1	NM_021930.6	c.465C>T	p.Ile155Ile	synonymous_variant	Exon 4 of 15	ENST00000257700.7	NP_068749.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RINT1	ENST00000257700.7	c.465C>T	p.Ile155Ile	synonymous_variant	Exon 4 of 15	1	NM_021930.6	ENSP00000257700.2

Frequencies

GnomAD3 genomes AF: 0.00631 AC: 959 AN: 152086 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.0104 AC: 2605 AN: 251328 Hom.: 42 AF XY: 0.00922 AC XY: 1252 AN XY: 135846

Gnomad AFR exome AF: 0.00338

Gnomad AMR exome AF: 0.0325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0294

Gnomad SAS exome AF: 0.00294

Gnomad FIN exome AF: 0.0222

Gnomad NFE exome AF: 0.00230

Gnomad OTH exome AF: 0.00913

GnomAD4 exome AF: 0.00471 AC: 6887 AN: 1461774 Hom.: 112 Cov.: 31 AF XY: 0.00454 AC XY: 3298 AN XY: 727184

Gnomad4 AFR exome AF: 0.00346

Gnomad4 AMR exome AF: 0.0302

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0490

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.0209

Gnomad4 NFE exome AF: 0.00163

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome AF: 0.00630 AC: 959 AN: 152202 Hom.: 16 Cov.: 31 AF XY: 0.00758 AC XY: 564 AN XY: 74436

Gnomad4 AFR AF: 0.00361

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0353

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.00200

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00591

Asia WGS AF: 0.0230 AC: 78 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jul 30, 2020

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

RINT1-related disorder Benign:1

Mar 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.3
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs79893877; hg19: chr7-105183046; COSMIC: COSV57561466; COSMIC: COSV57561466;