7-105542599-C-T

Position:

chr7-105542599-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.370

Variant links:

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]

RINT1 links:

RINT1 (HGNC:):

RINT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
RINT1	NM_021930.6 linkuse as main transcript	c.465C>T	p.Ile155Ile	synonymous_variant	4/15	ENST00000257700.7	NP_068749.3	Q6NUQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RINT1	ENST00000257700.7 linkuse as main transcript	c.465C>T	p.Ile155Ile	synonymous_variant	4/15	1	NM_021930.6	ENSP00000257700.2		Q6NUQ1

Frequencies

GnomAD3 genomes

AF:

0.00631

AC:

959

AN:

152086

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00922

AC XY:

1252

AN XY:

135846

show subpopulations

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.:

AF XY:

0.00454

AC XY:

3298

AN XY:

727184

show subpopulations

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.:

Cov.:

AF XY:

0.00758

AC XY:

564

AN XY:

74436

show subpopulations

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.:

Bravo

AF:

0.00591

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2020

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over