dbSNP rs892034: RINL:c.-166A>G (chr19-38878358-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.654

Publications

11 publications found

Variant links:

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]

RINL links:

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]

SIRT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RINL	NM_001195833.2 link	c.-166A>G		upstream_gene_variant		ENST00000591812.2	NP_001182762.1
SIRT2	NM_012237.4 link	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 link	c.-166A>G		upstream_gene_variant		2	NM_001195833.2	ENSP00000467107.1
SIRT2	ENST00000249396.12 link	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.:

show subpopulations

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.:

Cov.:

AF XY:

0.560

AC XY:

AN XY:

168

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.455

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.528

AC:

AN:

176

Other (OTH)

AF:

0.688

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.636

AC:

96652

AN:

151888

Hom.:

32922

Cov.:

AF XY:

0.638

AC XY:

47383

AN XY:

74210

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1607

3213

4820

6426

8033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.73

PhyloP100

-0.65

PromoterAI

0.038

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over