Variant 20-44771403-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_182970.4(RIMS4):c.108G>A(p.Arg36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,611,936 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 6 hom. )

Consequence

RIMS4
NM_182970.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

RIMS4 (HGNC:16183): (regulating synaptic membrane exocytosis 4) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in regulation of membrane potential; regulation of synapse organization; and regulation of synaptic vesicle exocytosis. Predicted to be located in synaptic membrane. Predicted to be active in glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

RIMS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 20-44771403-C-T is Benign according to our data. Variant chr20-44771403-C-T is described in ClinVar as [Benign]. Clinvar id is 783864.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.52 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00481 (733/152374) while in subpopulation AFR AF= 0.0168 (697/41588). AF 95% confidence interval is 0.0157. There are 3 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 733 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMS4	NM_182970.4 linkuse as main transcript	c.108G>A	p.Arg36=	synonymous_variant	2/6	ENST00000372851.8	NP_892015.1
RIMS4	NM_001205317.2 linkuse as main transcript	c.111G>A	p.Arg37=	synonymous_variant	2/6		NP_001192246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMS4	ENST00000372851.8 linkuse as main transcript	c.108G>A	p.Arg36=	synonymous_variant	2/6	1	NM_182970.4	ENSP00000361942	P4	Q9H426-1
RIMS4	ENST00000541604.2 linkuse as main transcript	c.111G>A	p.Arg37=	synonymous_variant	2/6	1		ENSP00000439287	A1	Q9H426-2

Frequencies

GnomAD3 genomes

AF:

0.00481

AC:

732

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00128

AC:

320

AN:

249634

Hom.:

AF XY:

0.000940

AC XY:

127

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000503

AC:

734

AN:

1459562

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

313

AN XY:

725804

show subpopulations

Gnomad4 AFR exome

AF:

0.0179

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00481

AC:

733

AN:

152374

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

346

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00539

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over