chr7-105565281-T-C

Variant names:

• chr7-105565281-T-C
• rs763828038
• NM_021930.6:c.1891T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021930.6(RINT1):​c.1891T>C​(p.Leu631Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RINT1 NM_021930.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.27
• Publications: 2 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]

EFCAB10 (HGNC:34531): (EF-hand calcium binding domain 10) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 7-105565281-T-C is Benign according to our data. Variant chr7-105565281-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1782083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.27 with no splicing effect.

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.1891T>C	p.Leu631Leu	synonymous	Exon 13 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.*166A>G		3_prime_UTR	Exon 5 of 5	NP_001342455.1	A6NFE3
	RINT1	NM_001346599.2		c.1657T>C	p.Leu553Leu	synonymous	Exon 13 of 15	NP_001333528.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.1891T>C	p.Leu631Leu	synonymous	Exon 13 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.*166A>G		3_prime_UTR	Exon 5 of 5	ENSP00000418678.1	A6NFE3
	RINT1	ENST00000967558.1		c.1996T>C	p.Leu666Leu	synonymous	Exon 13 of 15	ENSP00000637617.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 236720 AF XY: 0.00000782

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000140 AC: 2 AN: 1432014 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 2 AN XY: 708238

African (AFR) AF: 0.00 AC: 0 AN: 32372

American (AMR) AF: 0.00 AC: 0 AN: 39410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39248

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095448

Other (OTH) AF: 0.00 AC: 0 AN: 59028

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.24
DANN	Benign	0.75
PhyloP100		-2.3

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: rs763828038; hg19: chr7-105205728; COSMIC: COSV99994270; COSMIC: COSV99994270;