Genetic Variant RPL7L1:p.His66Arg (chr6-42883500-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001366481.3(RPL7L1):c.197A>G(p.His66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,609,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RPL7L1
NM_001366481.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

1 publications found

Variant links:

Genes affected

RPL7L1 (HGNC:21370): (ribosomal protein L7 like 1) Enables RNA binding activity. Predicted to be involved in maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to act upstream of or within blastocyst formation. Predicted to be located in nucleolus. Predicted to be part of cytosolic large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

RPL7L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02717343).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366481.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL7L1	NM_001366481.3	MANE Select	c.197A>G	p.His66Arg	missense	Exon 3 of 6	NP_001353410.1	Q6DKI1-1
RPL7L1	NM_198486.5		c.197A>G	p.His66Arg	missense	Exon 3 of 7	NP_940888.3	Q6DKI1-1
RPL7L1	NR_134562.3		n.608A>G		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL7L1	ENST00000493763.7	TSL:1 MANE Select	c.197A>G	p.His66Arg	missense	Exon 3 of 6	ENSP00000418221.3	Q6DKI1-1
RPL7L1	ENST00000304734.9	TSL:1	c.197A>G	p.His66Arg	missense	Exon 3 of 7	ENSP00000346063.4	Q6DKI1-1
RPL7L1	ENST00000397415.7	TSL:1	n.585A>G		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000283

AC:

AN:

247760

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1457110

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724846

show subpopulations

African (AFR)

AF:

0.000270

AC:

AN:

33296

American (AMR)

AF:

0.0000228

AC:

AN:

43884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25906

East Asian (EAS)

AF:

0.000252

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109764

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000105

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.6

(source)

DANN

Benign

0.62

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.52

M_CAP

Benign

0.0034

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.98

PhyloP100

1.6

PrimateAI

Benign

0.35

REVEL

Benign

0.010

MVP

0.37

MPC

0.38

ClinPred

0.0099

GERP RS

2.2

gMVP

0.39

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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