6-72354807-C-T

Position:

• chr6-72354807-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.4366+20972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,108 control chromosomes in the GnomAD database, including 47,732 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 0.79 (47732 hom., cov: 33)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.4366+20972C>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.4366+20972C>T		intron_variant		1	NM_014989.7	ENSP00000428417.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119395 AN: 151990 Hom.: 47673 Cov.: 33

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.786 AC: 119514 AN: 152108 Hom.: 47732 Cov.: 33 AF XY: 0.780 AC XY: 57953 AN XY: 74340

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.797

Alfa AF: 0.737 Hom.: 18916

Bravo AF: 0.801

Asia WGS AF: 0.774 AC: 2690 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.19

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: rs1934124; hg19: chr6-73064509; COSMIC: COSV53480126;