chr6-72182680-G-A

Variant names:

• chr6-72182680-G-A
• rs114505309
• NM_014989.7:c.1209G>A

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.1209G>A​(p.Ala403Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,445,990 control chromosomes in the GnomAD database, including 91,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6872 hom., cov: 32)
  • Exomes 𝑓: 0.36 (85013 hom.)
• Consequence: RIMS1 NM_014989.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.39
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 6-72182680-G-A is Benign according to our data. Variant chr6-72182680-G-A is described in ClinVar as Benign. ClinVar VariationId is 95656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	NM_014989.7	MANE Select	c.1209G>A	p.Ala403Ala	synonymous	Exon 6 of 34	NP_055804.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.1209G>A	p.Ala403Ala	synonymous	Exon 6 of 34	ENSP00000428417.1	Q86UR5-1
	RIMS1	ENST00000264839.11	TSL:5	c.1209G>A	p.Ala403Ala	synonymous	Exon 6 of 30	ENSP00000264839.7	Q86UR5-4
	RIMS1	ENST00000697193.1		c.1209G>A	p.Ala403Ala	synonymous	Exon 6 of 29	ENSP00000513179.1	A0A8V8TKU9

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42418 AN: 151314 Hom.: 6879 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.455 AC: 26400 AN: 57980 AF XY: 0.450

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.455

GnomAD4 exome AF: 0.358 AC: 463780 AN: 1294568 Hom.: 85013 Cov.: 38 AF XY: 0.358 AC XY: 226865 AN XY: 634486

African (AFR) AF: 0.118 AC: 2960 AN: 25046

American (AMR) AF: 0.397 AC: 8080 AN: 20350

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 6854 AN: 19500

East Asian (EAS) AF: 0.135 AC: 4057 AN: 30064

South Asian (SAS) AF: 0.317 AC: 19490 AN: 61444

European-Finnish (FIN) AF: 0.392 AC: 16413 AN: 41910

Middle Eastern (MID) AF: 0.291 AC: 1146 AN: 3940

European-Non Finnish (NFE) AF: 0.372 AC: 386852 AN: 1039090

Other (OTH) AF: 0.337 AC: 17928 AN: 53224

GnomAD4 genome AF: 0.280 AC: 42413 AN: 151422 Hom.: 6872 Cov.: 32 AF XY: 0.282 AC XY: 20850 AN XY: 73990

African (AFR) AF: 0.117 AC: 4865 AN: 41424

American (AMR) AF: 0.307 AC: 4671 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3466

East Asian (EAS) AF: 0.159 AC: 814 AN: 5130

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4820

European-Finnish (FIN) AF: 0.374 AC: 3861 AN: 10332

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.365 AC: 24705 AN: 67734

Other (OTH) AF: 0.285 AC: 599 AN: 2100

Alfa AF: 0.324 Hom.: 1146

Bravo AF: 0.266

Asia WGS AF: 0.201 AC: 695 AN: 3460

ClinVar

ClinVar submissions

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	-0.49
CADD	Benign	12
DANN	Uncertain	0.98
PhyloP100		1.4
PromoterAI		-0.055	Neutral
Mutation Taster		=100/0	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: rs114505309; hg19: chr6-72892383; COSMIC: COSV53439155; COSMIC: COSV53439155;