chr6-71956649-C-T

Variant names:

• chr6-71956649-C-T
• rs1936022
• NM_014989.7:c.165-12334C>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.165-12334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,932 control chromosomes in the GnomAD database, including 11,866 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 0.39 (11866 hom., cov: 32)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• 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, 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.165-12334C>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.165-12334C>T		intron_variant	Intron 1 of 33	1	NM_014989.7	ENSP00000428417.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58968 AN: 151812 Hom.: 11854 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.388 AC: 59008 AN: 151932 Hom.: 11866 Cov.: 32 AF XY: 0.396 AC XY: 29401 AN XY: 74256

African (AFR) AF: 0.306 AC: 12679 AN: 41450

American (AMR) AF: 0.451 AC: 6891 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3470

East Asian (EAS) AF: 0.509 AC: 2625 AN: 5156

South Asian (SAS) AF: 0.388 AC: 1863 AN: 4806

European-Finnish (FIN) AF: 0.510 AC: 5377 AN: 10542

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26637 AN: 67924

Other (OTH) AF: 0.402 AC: 849 AN: 2110

Alfa AF: 0.388 Hom.: 48259

Bravo AF: 0.382

Asia WGS AF: 0.474 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.060
DANN	Benign	0.85
PhyloP100		-2.9
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: rs1936022; hg19: chr6-72666352;