rs374498388

chr7-105532811-GTTC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_021930.6(RINT1):c.43-5_43-3del 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 0.00138 in 1,614,026 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (11 hom.)
• Consequence: RINT1 NM_021930.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.06

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 -16 ACMG points.

• BP6: Variant 7-105532811-GTTC-G is Benign according to our data. Variant chr7-105532811-GTTC-G is described in ClinVar as [Benign]. Clinvar id is 241409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00766 (1167/152256) while in subpopulation AFR AF= 0.0264 (1098/41542). AF 95% confidence interval is 0.0251. There are 13 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RINT1	NM_021930.6	c.43-5_43-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000257700.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RINT1	ENST00000257700.7	c.43-5_43-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021930.6	P1

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1165 AN: 152138 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00197 AC: 496 AN: 251464 Hom.: 5 AF XY: 0.00149 AC XY: 203 AN XY: 135914

Gnomad AFR exome AF: 0.0269

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000727 AC: 1063 AN: 1461770 Hom.: 11 AF XY: 0.000606 AC XY: 441 AN XY: 727196

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000567

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.00766 AC: 1167 AN: 152256 Hom.: 13 Cov.: 32 AF XY: 0.00755 AC XY: 562 AN XY: 74442

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.00321

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00421 Hom.: 1

Bravo AF: 0.00864

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

RINT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs374498388; hg19: chr7-105173258;