rs77121218

Variant names:

• chr6-72235647-G-A
• rs77121218
• NM_014989.7:c.1776G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-72235647-G-A
• chr6-72235647-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The NM_014989.7(RIMS1):​c.1776G>A​(p.Glu592Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,610,726 control chromosomes in the GnomAD database, including 217 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (25 hom., cov: 32)
  • Exomes 𝑓: 0.015 (192 hom.)
• Consequence: RIMS1 NM_014989.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: 1.22
• Publications: 10 publications found

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]

RIMS1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 7

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant 6-72235647-G-A is Benign according to our data. Variant chr6-72235647-G-A is described in ClinVar as Benign. ClinVar VariationId is 260494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0172 (2620/152100) while in subpopulation AFR AF = 0.0237 (984/41504). AF 95% confidence interval is 0.0225. There are 25 homozygotes in GnomAd4. There are 1252 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2620 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014989.7. 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
	RIMS1	NM_014989.7	MANE Select	c.1776G>A	p.Glu592Glu	synonymous	Exon 8 of 34	NP_055804.2
	RIMS1	NM_001350436.2		c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 27	NP_001337365.1
	RIMS1	NM_001350446.2		c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 26	NP_001337375.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.1776G>A	p.Glu592Glu	synonymous	Exon 8 of 34	ENSP00000428417.1	Q86UR5-1
	RIMS1	ENST00000425662.6	TSL:1	c.-46G>A		5_prime_UTR	Exon 3 of 22	ENSP00000411235.2	Q86UR5-10
	RIMS1	ENST00000524197.1	TSL:1	n.582G>A		non_coding_transcript_exon	Exon 3 of 15

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2622 AN: 151982 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.0129 AC: 3163 AN: 245860 AF XY: 0.0123

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.00522

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0172

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0107

GnomAD4 exome AF: 0.0150 AC: 21882 AN: 1458626 Hom.: 192 Cov.: 29 AF XY: 0.0148 AC XY: 10723 AN XY: 725400

African (AFR) AF: 0.0234 AC: 782 AN: 33378

American (AMR) AF: 0.00522 AC: 232 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00933 AC: 243 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00567 AC: 486 AN: 85658

European-Finnish (FIN) AF: 0.0161 AC: 860 AN: 53300

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5760

European-Non Finnish (NFE) AF: 0.0166 AC: 18460 AN: 1110196

Other (OTH) AF: 0.0134 AC: 805 AN: 60276

GnomAD4 genome AF: 0.0172 AC: 2620 AN: 152100 Hom.: 25 Cov.: 32 AF XY: 0.0168 AC XY: 1252 AN XY: 74352

African (AFR) AF: 0.0237 AC: 984 AN: 41504

American (AMR) AF: 0.0122 AC: 186 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00540 AC: 26 AN: 4818

European-Finnish (FIN) AF: 0.0177 AC: 188 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1172 AN: 67960

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.0152 Hom.: 12

Bravo AF: 0.0163

Asia WGS AF: 0.00664 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 7 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	1	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	4.4
DANN	Benign	0.50
PhyloP100		1.2
Mutation Taster		=87/13	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: rs77121218; hg19: chr6-72945350; COSMIC: COSV53488244;