Genetic Variant NM_145058.3:c.81G>C (chr12-123436340-C-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_145058.3(RILPL2):c.81G>C(p.Gly27Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 1,565,056 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 79 hom. )

Consequence

RILPL2
NM_145058.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.482

Publications

3 publications found

Variant links:

Genes affected

RILPL2 (HGNC:28787): (Rab interacting lysosomal protein like 2) This gene encodes a protein that contains a rab-interacting lysosomal protein-like domain. This protein may be involved in regulating lysosome morphology. This protein may also be a target for the Hepatitis C virus and assist in viral replication. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

RILPL2 links:

ENSG00000296923 (HGNC:):

ENSG00000296923 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 12-123436340-C-G is Benign according to our data. Variant chr12-123436340-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2643510.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.482 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145058.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RILPL2	NM_145058.3	MANE Select	c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 4	NP_659495.1	Q969X0
	RILPL2	NR_130703.2		n.345G>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RILPL2	ENST00000280571.10	TSL:1 MANE Select	c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 4	ENSP00000280571.8	Q969X0
RILPL2	ENST00000718483.1		c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 4	ENSP00000520843.1	A0ABB0MVJ7
RILPL2	ENST00000718482.1		c.81G>C	p.Gly27Gly	synonymous	Exon 1 of 4	ENSP00000520842.1	A0ABB0MVH7

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

771

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00878

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00552

AC:

940

AN:

170240

AF XY:

0.00573

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.0000814

Gnomad FIN exome

AF:

0.00524

Gnomad NFE exome

AF:

0.00933

Gnomad OTH exome

AF:

0.00509

GnomAD4 exome

AF:

0.00931

AC:

13153

AN:

1412720

Hom.:

Cov.:

AF XY:

0.00919

AC XY:

6420

AN XY:

698266

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

32160

American (AMR)

AF:

0.00268

AC:

AN:

36904

Ashkenazi Jewish (ASJ)

AF:

0.00509

AC:

129

AN:

25320

East Asian (EAS)

AF:

0.0000273

AC:

AN:

36672

South Asian (SAS)

AF:

0.00262

AC:

211

AN:

80536

European-Finnish (FIN)

AF:

0.00565

AC:

282

AN:

49950

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.0110

AC:

11921

AN:

1086834

Other (OTH)

AF:

0.00780

AC:

457

AN:

58624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

808

1615

2423

3230

4038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.00505

AC:

769

AN:

152336

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

317

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41578

American (AMR)

AF:

0.00235

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00878

AC:

597

AN:

68014

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00743

Hom.:

Bravo

AF:

0.00508

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.4

(source)

DANN

Benign

0.92

PhyloP100

-0.48

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over