6-71998178-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014989.7(RIMS1):c.245+29115T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 152,052 control chromosomes in the GnomAD database, including 3 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 0.0047 (3 hom., cov: 31)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd at 716 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIMS1	NM_014989.7	c.245+29115T>G		intron_variant		ENST00000521978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIMS1	ENST00000521978.6	c.245+29115T>G		intron_variant		1	NM_014989.7	A2

Frequencies

GnomAD3 genomes AF: 0.00471 AC: 716 AN: 151934 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00731

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00470 AC: 715 AN: 152052 Hom.: 3 Cov.: 31 AF XY: 0.00478 AC XY: 355 AN XY: 74310

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.00730

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000471 Hom.: 1790

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.23
Dann	Benign	0.68

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: rs502046; hg19: chr6-72707881;