rs36058979

Variant names:

• chr7-105567302-T-C
• rs36058979
• NM_021930.6:c.2370T>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.2370T>C​(p.Thr790Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,586,976 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (49 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (61 hom.)
• Consequence: RINT1 NM_021930.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0100
• 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]

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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-105567302-T-C is Benign according to our data. Variant chr7-105567302-T-C is described in ClinVar as Benign. ClinVar VariationId is 224935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 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.2370T>C	p.Thr790Thr	synonymous	Exon 15 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.383+165A>G		intron	N/A	NP_001342455.1	A6NFE3
	RINT1	NM_001346599.2		c.2136T>C	p.Thr712Thr	synonymous	Exon 15 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.2370T>C	p.Thr790Thr	synonymous	Exon 15 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000486180.5	TSL:1	c.*152A>G		3_prime_UTR	Exon 4 of 4	ENSP00000417484.1	J3KR48
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.383+165A>G		intron	N/A	ENSP00000418678.1	A6NFE3

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152226 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00410 AC: 948 AN: 230942 AF XY: 0.00271

Gnomad AFR exome AF: 0.0556

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000462

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00146 AC: 2093 AN: 1434632 Hom.: 61 Cov.: 28 AF XY: 0.00125 AC XY: 887 AN XY: 711972

African (AFR) AF: 0.0570 AC: 1830 AN: 32130

American (AMR) AF: 0.00174 AC: 68 AN: 39044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.0000489 AC: 4 AN: 81784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5648

European-Non Finnish (NFE) AF: 0.0000155 AC: 17 AN: 1099032

Other (OTH) AF: 0.00288 AC: 171 AN: 59282

GnomAD4 genome AF: 0.0149 AC: 2264 AN: 152344 Hom.: 49 Cov.: 32 AF XY: 0.0145 AC XY: 1078 AN XY: 74496

African (AFR) AF: 0.0524 AC: 2177 AN: 41580

American (AMR) AF: 0.00379 AC: 58 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00589 Hom.: 15

Bravo AF: 0.0166

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	RINT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.7
DANN	Benign	0.83
PhyloP100		-0.010
Mutation Taster		=98/2	polymorphism

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: rs36058979; hg19: chr7-105207749;