rs9341356

Variant names:

• chr6-71911084-G-T
• rs9341356
• NM_014989.7:c.164+23897G>T

Variant summary

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

The NM_014989.7(RIMS1):​c.164+23897G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 152,160 control chromosomes in the GnomAD database, including 482 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 0.067 (482 hom., cov: 32)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.164+23897G>T		intron_variant	Intron 1 of 33	ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.164+23897G>T		intron_variant	Intron 1 of 33	1	NM_014989.7	ENSP00000428417.1

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10240 AN: 152042 Hom.: 479 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0674 AC: 10248 AN: 152160 Hom.: 482 Cov.: 32 AF XY: 0.0673 AC XY: 5006 AN XY: 74378

African (AFR) AF: 0.0623 AC: 2588 AN: 41542

American (AMR) AF: 0.138 AC: 2113 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5156

South Asian (SAS) AF: 0.0442 AC: 213 AN: 4818

European-Finnish (FIN) AF: 0.0353 AC: 374 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3611 AN: 67996

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0596 Hom.: 718

Bravo AF: 0.0772

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.3
DANN	Benign	0.74
PhyloP100		0.39
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: rs9341356; hg19: chr6-72620787;