rs892034

Variant names:

• chr19-38878358-T-C
• rs892034
• NM_001195833.2:c.-166A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-38878358-T-C
• chr19-38878358-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195833.2(RINL):​c.-166A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,118 control chromosomes in the GnomAD database, including 32,960 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 0.64 (32922 hom., cov: 30)
  • Exomes 𝑓: 0.55 (38 hom.)
• Consequence: RINL NM_001195833.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

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]

SIRT2 (HGNC:10886): (sirtuin 2) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RINL	NM_001195833.2	c.-166A>G		upstream_gene_variant		ENST00000591812.2	NP_001182762.1
SIRT2	NM_012237.4	c.*797A>G		downstream_gene_variant		ENST00000249396.12	NP_036369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RINL	ENST00000591812.2	c.-166A>G		upstream_gene_variant		2	NM_001195833.2	ENSP00000467107.1
SIRT2	ENST00000249396.12	c.*797A>G		downstream_gene_variant		1	NM_012237.4	ENSP00000249396.7

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96529 AN: 151770 Hom.: 32858 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.548 AC: 126 AN: 230 Hom.: 38 Cov.: 0 AF XY: 0.560 AC XY: 94 AN XY: 168

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.636 AC: 96652 AN: 151888 Hom.: 32922 Cov.: 30 AF XY: 0.638 AC XY: 47383 AN XY: 74210

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.620

Alfa AF: 0.529 Hom.: 23896

Bravo AF: 0.658

Asia WGS AF: 0.766 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs892034; hg19: chr19-39368998;