6-71886840-A-AAAG

Position:

• chr6-71886840-A-AAAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014989.7(RIMS1):​c.-182_-180dupAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 652,612 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (2 hom.)
• Consequence: RIMS1 NM_014989.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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.

• BP6: Variant 6-71886840-A-AAAG is Benign according to our data. Variant chr6-71886840-A-AAAG is described in ClinVar as [Likely_benign]. Clinvar id is 357823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0019 (289/152248) while in subpopulation AMR AF= 0.0174 (266/15308). AF 95% confidence interval is 0.0157. There are 6 homozygotes in gnomad4. There are 162 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 289 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.-182_-180dupAGA		5_prime_UTR_variant	1/34	ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.-182_-180dupAGA		5_prime_UTR_variant	1/34	1	NM_014989.7	ENSP00000428417.1
RIMS1	ENST00000697193.1	c.-182_-180dupAGA		5_prime_UTR_variant	1/29			ENSP00000513179.1
RIMS1	ENST00000491071.6	c.-182_-180dupAGA		5_prime_UTR_variant	1/28	5		ENSP00000430101.1
RIMS1	ENST00000370419.6	n.140_142dupAGA		non_coding_transcript_exon_variant	1/19	5

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152132 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000977 AC: 489 AN: 500364 Hom.: 2 Cov.: 6 AF XY: 0.000888 AC XY: 236 AN XY: 265660

Gnomad4 AFR exome AF: 0.000228

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000832

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000224

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152248 Hom.: 6 Cov.: 32 AF XY: 0.00218 AC XY: 162 AN XY: 74462

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00315

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone-Rod Dystrophy, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs555947867; hg19: chr6-72596543;