Genetic Variant LARP7:p.Glu4Lys (chr4-112644679-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016648.4(LARP7):c.10G>A(p.Glu4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,600,186 control chromosomes in the GnomAD database, including 2,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 209 hom., cov: 32)

Exomes 𝑓: 0.046 ( 2320 hom. )

Consequence

LARP7
NM_016648.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.57

Variant links:

Genes affected

LARP7 (HGNC:24912): (La ribonucleoprotein 7, transcriptional regulator) This gene encodes a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

LARP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015173256).

BP6

Variant 4-112644679-G-A is Benign according to our data. Variant chr4-112644679-G-A is described in ClinVar as [Benign]. Clinvar id is 129478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARP7	NM_016648.4 link	c.10G>A	p.Glu4Lys	missense_variant	Exon 2 of 13	ENST00000344442.10	NP_057732.2	Q4G0J3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARP7	ENST00000344442.10 link	c.10G>A	p.Glu4Lys	missense_variant	Exon 2 of 13	2	NM_016648.4	ENSP00000344950.5		Q4G0J3-1

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

6005

AN:

151802

Hom.:

209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.0525

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0255

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0336

GnomAD3 exomes

AF:

0.0603

AC:

14691

AN:

243820

Hom.:

706

AF XY:

0.0607

AC XY:

8031

AN XY:

132270

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0744

Gnomad ASJ exome

AF:

0.0574

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.0948

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0404

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.0463

AC:

67099

AN:

1448266

Hom.:

2320

Cov.:

AF XY:

0.0477

AC XY:

34386

AN XY:

720662

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.0686

Gnomad4 ASJ exome

AF:

0.0569

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.0954

Gnomad4 FIN exome

AF:

0.0252

Gnomad4 NFE exome

AF:

0.0386

Gnomad4 OTH exome

AF:

0.0498

GnomAD4 genome

AF:

0.0396

AC:

6013

AN:

151920

Hom.:

209

Cov.:

AF XY:

0.0409

AC XY:

3039

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0547

Gnomad4 ASJ

AF:

0.0525

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0255

Gnomad4 NFE

AF:

0.0398

Gnomad4 OTH

AF:

0.0365

Alfa

AF:

0.0463

Hom.:

315

Bravo

AF:

0.0403

TwinsUK

AF:

0.0402

AC:

149

ALSPAC

AF:

0.0343

AC:

132

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.0390

AC:

317

ExAC

AF:

0.0602

AC:

7267

Asia WGS

AF:

0.116

AC:

403

AN:

3476

EpiCase

AF:

0.0363

EpiControl

AF:

0.0379

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

.;.;T;T;T;.;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

.;T;T;T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.;.;.;L;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.068

T;T;T;T;T;T;T

Sift4G

Benign

0.099

T;T;T;T;T;T;T

Polyphen

0.60

P;.;.;.;P;P;.

Vest4

0.23

MPC

0.056

ClinPred

0.012

GERP RS

3.3

Varity_R

0.11

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over