6-72354807-C-T

Variant names:

• chr6-72354807-C-T
• rs1934124
• NM_014989.7:c.4366+20972C>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.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
• Publications: 1 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=-0.94).
• 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 rank	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.4366+20972C>T		intron_variant	Intron 29 of 33	ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.4366+20972C>T		intron_variant	Intron 29 of 33	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

African (AFR) AF: 0.942 AC: 39119 AN: 41532

American (AMR) AF: 0.721 AC: 11027 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3468

East Asian (EAS) AF: 0.826 AC: 4272 AN: 5172

South Asian (SAS) AF: 0.699 AC: 3376 AN: 4828

European-Finnish (FIN) AF: 0.663 AC: 6988 AN: 10536

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49518 AN: 67970

Other (OTH) AF: 0.797 AC: 1685 AN: 2114

Alfa AF: 0.737 Hom.: 21006

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
PhyloP100		-0.26
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: rs1934124; hg19: chr6-73064509; COSMIC: COSV53480126;