19-38870121-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001195833.2(RINL):c.1164G>A(p.Gly388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,421,752 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (4 hom.)
• Consequence: RINL NM_001195833.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.929

Genes affected

RINL (HGNC:24795): (Ras and Rab interactor like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in endocytosis. Predicted to be located in actin cytoskeleton and ruffle. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 19-38870121-C-T is Benign according to our data. Variant chr19-38870121-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.929 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RINL	NM_001195833.2	c.1164G>A	p.Gly388=	synonymous_variant	9/12	ENST00000591812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RINL	ENST00000591812.2	c.1164G>A	p.Gly388=	synonymous_variant	9/12	2	NM_001195833.2	P2
RINL	ENST00000598904.5	c.822G>A	p.Gly274=	synonymous_variant	8/11	5		A2
RINL	ENST00000589111.5	n.1631G>A		non_coding_transcript_exon_variant	6/9	2
	ENST00000593830.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00152 AC: 42 AN: 27584 Hom.: 0 AF XY: 0.00223 AC XY: 37 AN XY: 16620

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00695

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000377

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000461 AC: 585 AN: 1269442 Hom.: 4 Cov.: 34 AF XY: 0.000593 AC XY: 369 AN XY: 622076

Gnomad4 AFR exome AF: 0.0000803

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000528

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00531

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000198

Gnomad4 OTH exome AF: 0.000800

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74468

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00579

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000140

Asia WGS AF: 0.000868 AC: 3 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

RINL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	15
Dann	Benign	0.97

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: rs560514643; hg19: chr19-39360761; COSMIC: COSV61573582; COSMIC: COSV61573582;