6-71961862-C-T

Variant names:

• chr6-71961862-C-T
• rs1482567
• NM_014989.7:c.165-7121C>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.165-7121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,998 control chromosomes in the GnomAD database, including 31,872 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 0.65 (31872 hom., cov: 33)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 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.165-7121C>T		intron	N/A	NP_055804.2
	RIMS1	NM_001350413.1		c.165-7121C>T		intron	N/A	NP_001337342.1
	RIMS1	NM_001350411.1		c.165-7121C>T		intron	N/A	NP_001337340.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.165-7121C>T		intron	N/A	ENSP00000428417.1	Q86UR5-1
	RIMS1	ENST00000264839.11	TSL:5	c.165-7121C>T		intron	N/A	ENSP00000264839.7	Q86UR5-4
	RIMS1	ENST00000697193.1		c.165-7121C>T		intron	N/A	ENSP00000513179.1	A0A8V8TKU9

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98073 AN: 151880 Hom.: 31842 Cov.: 33

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.646 AC: 98152 AN: 151998 Hom.: 31872 Cov.: 33 AF XY: 0.649 AC XY: 48204 AN XY: 74308

African (AFR) AF: 0.626 AC: 25958 AN: 41464

American (AMR) AF: 0.729 AC: 11120 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2343 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3735 AN: 5180

South Asian (SAS) AF: 0.541 AC: 2609 AN: 4822

European-Finnish (FIN) AF: 0.690 AC: 7291 AN: 10570

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.630 AC: 42816 AN: 67916

Other (OTH) AF: 0.657 AC: 1384 AN: 2108

Alfa AF: 0.631 Hom.: 41449

Bravo AF: 0.651

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.4
DANN	Benign	0.43
PhyloP100		0.28
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: rs1482567; hg19: chr6-72671565;