NM_014989.7:c.246-49854C>A

Variant names:

• chr6-72047095-C-A
• rs484596
• NM_014989.7:c.246-49854C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014989.7(RIMS1):​c.246-49854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,944 control chromosomes in the GnomAD database, including 15,453 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15453 hom., cov: 32)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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.246-49854C>A		intron	N/A	NP_055804.2
	RIMS1	NM_001350413.1		c.246-49854C>A		intron	N/A	NP_001337342.1
	RIMS1	NM_001350411.1		c.246-49857C>A		intron	N/A	NP_001337340.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.246-49854C>A		intron	N/A	ENSP00000428417.1
	RIMS1	ENST00000264839.11	TSL:5	c.246-49854C>A		intron	N/A	ENSP00000264839.7
	RIMS1	ENST00000697193.1		c.246-49854C>A		intron	N/A	ENSP00000513179.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67649 AN: 151824 Hom.: 15437 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67710 AN: 151944 Hom.: 15453 Cov.: 32 AF XY: 0.446 AC XY: 33151 AN XY: 74270

African (AFR) AF: 0.540 AC: 22376 AN: 41430

American (AMR) AF: 0.443 AC: 6758 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3466

East Asian (EAS) AF: 0.663 AC: 3425 AN: 5168

South Asian (SAS) AF: 0.440 AC: 2120 AN: 4822

European-Finnish (FIN) AF: 0.377 AC: 3981 AN: 10556

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26196 AN: 67942

Other (OTH) AF: 0.444 AC: 935 AN: 2106

Alfa AF: 0.397 Hom.: 2446

Bravo AF: 0.457

Asia WGS AF: 0.534 AC: 1851 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		-0.40
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: rs484596; hg19: chr6-72756798;