7-105565310-A-C

Variant names:

• chr7-105565310-A-C
• rs2133475535
• NM_021930.6:c.1920A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021930.6(RINT1):​c.1920A>C​(p.Ala640Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A640A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RINT1 NM_021930.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.318 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.1920A>C	p.Ala640Ala	synonymous	Exon 13 of 15	NP_068749.3
	EFCAB10	NM_001355526.2	MANE Select	c.*137T>G		3_prime_UTR	Exon 5 of 5	NP_001342455.1	A6NFE3
	RINT1	NM_001346599.2		c.1686A>C	p.Ala562Ala	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.1920A>C	p.Ala640Ala	synonymous	Exon 13 of 15	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.*137T>G		3_prime_UTR	Exon 5 of 5	ENSP00000418678.1	A6NFE3
	RINT1	ENST00000967558.1		c.2025A>C	p.Ala675Ala	synonymous	Exon 13 of 15	ENSP00000637617.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460836 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726532

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111132

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.41
DANN	Benign	0.73
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2133475535; hg19: chr7-105205757;