6-71961862-C-T

Position:

• chr6-71961862-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.165-7121C>T		intron_variant		ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.165-7121C>T		intron_variant		1	NM_014989.7	ENSP00000428417.1

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

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.657

Alfa AF: 0.629 Hom.: 35632

Bravo AF: 0.651

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.4
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1482567; hg19: chr6-72671565;