rs117732387

Variant names:

• chr7-105551717-T-C
• rs117732387
• NM_021930.6:c.1471+10T>C

Variant summary

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

The NM_021930.6(RINT1):​c.1471+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,579,480 control chromosomes in the GnomAD database, including 350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (293 hom.)
• Consequence: RINT1 NM_021930.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.291
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• infantile liver failure syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• infantile liver failure syndrome 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-105551717-T-C is Benign according to our data. Variant chr7-105551717-T-C is described in ClinVar as Benign. ClinVar VariationId is 416391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021930.6. 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
	RINT1	NM_021930.6	MANE Select	c.1471+10T>C		intron	N/A	NP_068749.3
	RINT1	NM_001346599.2		c.1237+10T>C		intron	N/A	NP_001333528.1
	RINT1	NM_001346601.2		c.547+10T>C		intron	N/A	NP_001333530.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.1471+10T>C		intron	N/A	ENSP00000257700.2	Q6NUQ1
	RINT1	ENST00000967558.1		c.1600+10T>C		intron	N/A	ENSP00000637617.1
	RINT1	ENST00000899074.1		c.1471+10T>C		intron	N/A	ENSP00000569133.1

Frequencies

GnomAD3 genomes AF: 0.00987 AC: 1502 AN: 152208 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0163 AC: 3663 AN: 224890 AF XY: 0.0136

Gnomad AFR exome AF: 0.00161

Gnomad AMR exome AF: 0.0867

Gnomad ASJ exome AF: 0.000469

Gnomad EAS exome AF: 0.0719

Gnomad FIN exome AF: 0.0000473

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.0136

GnomAD4 exome AF: 0.00496 AC: 7084 AN: 1427154 Hom.: 293 Cov.: 27 AF XY: 0.00460 AC XY: 3261 AN XY: 709088

African (AFR) AF: 0.00110 AC: 35 AN: 31890

American (AMR) AF: 0.0840 AC: 3103 AN: 36936

Ashkenazi Jewish (ASJ) AF: 0.000808 AC: 20 AN: 24738

East Asian (EAS) AF: 0.0774 AC: 3018 AN: 38998

South Asian (SAS) AF: 0.00293 AC: 236 AN: 80504

European-Finnish (FIN) AF: 0.0000567 AC: 3 AN: 52868

Middle Eastern (MID) AF: 0.000892 AC: 5 AN: 5604

European-Non Finnish (NFE) AF: 0.000217 AC: 238 AN: 1096774

Other (OTH) AF: 0.00724 AC: 426 AN: 58842

GnomAD4 genome AF: 0.00997 AC: 1518 AN: 152326 Hom.: 57 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74494

African (AFR) AF: 0.00176 AC: 73 AN: 41574

American (AMR) AF: 0.0648 AC: 991 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.0716 AC: 371 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68032

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00406 Hom.: 11

Bravo AF: 0.0148

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	6.9
DANN	Benign	0.55
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs117732387; hg19: chr7-105192164; COSMIC: COSV57559957; COSMIC: COSV57559957;