NM_014989.7:c.1083A>G

Variant names:

• chr6-72182554-A-G
• rs2463730
• NM_014989.7:c.1083A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014989.7(RIMS1):​c.1083A>G​(p.Leu361Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,552,564 control chromosomes in the GnomAD database, including 769,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72743 hom., cov: 33)
  • Exomes 𝑓: 1.0 (697126 hom.)
• Consequence: RIMS1 NM_014989.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.948
• Publications: 15 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, Ambry Genetics, Illumina, 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-72182554-A-G is Benign according to our data. Variant chr6-72182554-A-G is described in ClinVar as Benign. ClinVar VariationId is 95655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.948 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	NM_014989.7	MANE Select	c.1083A>G	p.Leu361Leu	synonymous	Exon 6 of 34	NP_055804.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.1083A>G	p.Leu361Leu	synonymous	Exon 6 of 34	ENSP00000428417.1
	RIMS1	ENST00000264839.11	TSL:5	c.1083A>G	p.Leu361Leu	synonymous	Exon 6 of 30	ENSP00000264839.7
	RIMS1	ENST00000697193.1		c.1083A>G	p.Leu361Leu	synonymous	Exon 6 of 29	ENSP00000513179.1

Frequencies

GnomAD3 genomes AF: 0.977 AC: 148643 AN: 152142 Hom.: 72692 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.983

GnomAD2 exomes AF: 0.995 AC: 156386 AN: 157178 AF XY: 0.996

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.998 AC: 1397186 AN: 1400304 Hom.: 697126 Cov.: 70 AF XY: 0.998 AC XY: 689538 AN XY: 690868

African (AFR) AF: 0.922 AC: 29171 AN: 31648

American (AMR) AF: 0.995 AC: 35684 AN: 35880

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25206 AN: 25206

East Asian (EAS) AF: 1.00 AC: 35856 AN: 35856

South Asian (SAS) AF: 1.00 AC: 79417 AN: 79434

European-Finnish (FIN) AF: 1.00 AC: 49026 AN: 49026

Middle Eastern (MID) AF: 0.997 AC: 4371 AN: 4386

European-Non Finnish (NFE) AF: 1.00 AC: 1080707 AN: 1080804

Other (OTH) AF: 0.995 AC: 57748 AN: 58064

GnomAD4 genome AF: 0.977 AC: 148752 AN: 152260 Hom.: 72743 Cov.: 33 AF XY: 0.977 AC XY: 72783 AN XY: 74462

African (AFR) AF: 0.921 AC: 38249 AN: 41552

American (AMR) AF: 0.990 AC: 15159 AN: 15310

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5164

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67985 AN: 68002

Other (OTH) AF: 0.983 AC: 2076 AN: 2112

Alfa AF: 0.989 Hom.: 38015

Bravo AF: 0.973

Asia WGS AF: 0.997 AC: 3468 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cone-rod dystrophy 7 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		0.95
PromoterAI		0.00020	Neutral
Mutation Taster		=97/3	polymorphism (auto)

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: rs2463730; hg19: chr6-72892257; COSMIC: COSV53453426; COSMIC: COSV53453426;