chr6-72261430-A-G

Variant names:

• chr6-72261430-A-G
• rs10455255
• NM_014989.7:c.3116+663A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014989.7(RIMS1):​c.3116+663A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 984,808 control chromosomes in the GnomAD database, including 5,430 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 0.092 (819 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4611 hom.)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014989.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	NM_014989.7	MANE Select	c.3116+663A>G		intron	N/A	NP_055804.2
	RIMS1	NM_001350436.2		c.1535+663A>G		intron	N/A	NP_001337365.1
	RIMS1	NM_001350446.2		c.1538+663A>G		intron	N/A	NP_001337375.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMS1	ENST00000521978.6	TSL:1 MANE Select	c.3116+663A>G		intron	N/A	ENSP00000428417.1
	RIMS1	ENST00000425662.6	TSL:1	c.1295+663A>G		intron	N/A	ENSP00000411235.2
	RIMS1	ENST00000370420.8	TSL:1	c.791+663A>G		intron	N/A	ENSP00000359448.4

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13968 AN: 152054 Hom.: 813 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0968

GnomAD4 exome AF: 0.103 AC: 85385 AN: 832636 Hom.: 4611 Cov.: 28 AF XY: 0.103 AC XY: 39487 AN XY: 384536

African (AFR) AF: 0.0120 AC: 189 AN: 15784

American (AMR) AF: 0.166 AC: 167 AN: 1004

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 774 AN: 5144

East Asian (EAS) AF: 0.135 AC: 488 AN: 3628

South Asian (SAS) AF: 0.137 AC: 2256 AN: 16456

European-Finnish (FIN) AF: 0.141 AC: 39 AN: 276

Middle Eastern (MID) AF: 0.101 AC: 164 AN: 1620

European-Non Finnish (NFE) AF: 0.103 AC: 78338 AN: 761430

Other (OTH) AF: 0.109 AC: 2970 AN: 27294

GnomAD4 genome AF: 0.0919 AC: 13979 AN: 152172 Hom.: 819 Cov.: 32 AF XY: 0.0944 AC XY: 7025 AN XY: 74388

African (AFR) AF: 0.0193 AC: 802 AN: 41568

American (AMR) AF: 0.134 AC: 2039 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.144 AC: 744 AN: 5174

South Asian (SAS) AF: 0.143 AC: 692 AN: 4828

European-Finnish (FIN) AF: 0.146 AC: 1546 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7272 AN: 67982

Other (OTH) AF: 0.102 AC: 215 AN: 2108

Alfa AF: 0.0975 Hom.: 111

Bravo AF: 0.0882

Asia WGS AF: 0.129 AC: 446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.36
PhyloP100		1.0
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: rs10455255; hg19: chr6-72971133;