6-71886722-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014989.7(RIMS1):c.-302C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00096 in 185,472 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: RIMS1 NM_014989.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.345

Genes affected

RIMS1 (HGNC:17282): (regulating synaptic membrane exocytosis 1) The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-71886722-C-T is Benign according to our data. Variant chr6-71886722-C-T is described in ClinVar as [Benign]. Clinvar id is 357821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS1	NM_014989.7	c.-302C>T		5_prime_UTR_variant	1/34	ENST00000521978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS1	ENST00000521978.6	c.-302C>T		5_prime_UTR_variant	1/34	1	NM_014989.7	A2
RIMS1	ENST00000491071.6	c.-302C>T		5_prime_UTR_variant	1/28	5
RIMS1	ENST00000697193.1	c.-302C>T		5_prime_UTR_variant	1/29			P3
RIMS1	ENST00000370419.6	n.20C>T		non_coding_transcript_exon_variant	1/19	5

Frequencies

GnomAD3 genomes AF: 0.000881 AC: 133 AN: 151048 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000975

Gnomad OTH AF: 0.00193

GnomAD4 exome AF: 0.00128 AC: 44 AN: 34314 Hom.: 1 Cov.: 0 AF XY: 0.00125 AC XY: 22 AN XY: 17548

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00156

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00836

Gnomad4 FIN exome AF: 0.000373

Gnomad4 NFE exome AF: 0.000952

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome AF: 0.000886 AC: 134 AN: 151158 Hom.: 1 Cov.: 32 AF XY: 0.000826 AC XY: 61 AN XY: 73846

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00119

Gnomad4 ASJ AF: 0.00145

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000976

Gnomad4 OTH AF: 0.00191

Bravo AF: 0.000793

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone-rod dystrophy 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	14
Dann	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs577898637; hg19: chr6-72596425;