NM_001195833.2:c.-166A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195833.2. 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
	RINL	NM_001195833.2	MANE Select	c.-166A>G		upstream_gene	N/A	NP_001182762.1
	SIRT2	NM_012237.4	MANE Select	c.*797A>G		downstream_gene	N/A	NP_036369.2
	RINL	NM_198445.4		c.-492A>G		upstream_gene	N/A	NP_940847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RINL	ENST00000591812.2	TSL:2 MANE Select	c.-166A>G		upstream_gene	N/A	ENSP00000467107.1
	SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.*797A>G		downstream_gene	N/A	ENSP00000249396.7
	SIRT2	ENST00000392081.6	TSL:1	c.*797A>G		downstream_gene	N/A	ENSP00000375931.2

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

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.455 AC: 10 AN: 22

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.528 AC: 93 AN: 176

Other (OTH) AF: 0.688 AC: 11 AN: 16

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

African (AFR) AF: 0.886 AC: 36780 AN: 41490

American (AMR) AF: 0.611 AC: 9333 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4465 AN: 5134

South Asian (SAS) AF: 0.572 AC: 2748 AN: 4806

European-Finnish (FIN) AF: 0.537 AC: 5669 AN: 10562

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33819 AN: 67846

Other (OTH) AF: 0.620 AC: 1308 AN: 2110

Alfa AF: 0.546 Hom.: 41106

Bravo AF: 0.658

Asia WGS AF: 0.766 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-0.65
PromoterAI		0.038	Neutral

Splicing

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

Other links and lift over

dbSNP: rs892034; hg19: chr19-39368998;