NM_016648.4:c.10G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

microcephalic primordial dwarfism, Alazami type
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

LARP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LARP7	NM_016648.4	MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 2 of 13	NP_057732.2	Q4G0J3-1
LARP7	NM_001370974.1		c.10G>A	p.Glu4Lys	missense	Exon 2 of 13	NP_001357903.1	A0A8Q3SHN7
LARP7	NM_001370975.1		c.10G>A	p.Glu4Lys	missense	Exon 2 of 13	NP_001357904.1	A0A8Q3SHN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LARP7	ENST00000344442.10	TSL:2 MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 2 of 13	ENSP00000344950.5	Q4G0J3-1
LARP7	ENST00000509061.5	TSL:1	c.10G>A	p.Glu4Lys	missense	Exon 4 of 15	ENSP00000422626.2	Q4G0J3-1
LARP7	ENST00000509622.5	TSL:1	n.10G>A		non_coding_transcript_exon	Exon 2 of 13	ENSP00000422451.1	D6RBH8

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

GnomAD2 exomes

AF:

0.0603

AC:

14691

AN:

243820

AF XY:

0.0607

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 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

African (AFR)

AF:

0.0108

AC:

357

AN:

32906

American (AMR)

AF:

0.0686

AC:

2990

AN:

43608

Ashkenazi Jewish (ASJ)

AF:

0.0569

AC:

1468

AN:

25778

East Asian (EAS)

AF:

0.180

AC:

7091

AN:

39352

South Asian (SAS)

AF:

0.0954

AC:

8020

AN:

84098

European-Finnish (FIN)

AF:

0.0252

AC:

1339

AN:

53138

Middle Eastern (MID)

AF:

0.0335

AC:

191

AN:

5706

European-Non Finnish (NFE)

AF:

0.0386

AC:

42667

AN:

1103980

Other (OTH)

AF:

0.0498

AC:

2976

AN:

59700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2665

5330

7994

10659

13324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1742

3484

5226

6968

8710

<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:

0.0396

AC:

6013

AN:

151920

Hom.:

209

Cov.:

AF XY:

0.0409

AC XY:

3039

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.0113

AC:

470

AN:

41478

American (AMR)

AF:

0.0547

AC:

836

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0525

AC:

182

AN:

3466

East Asian (EAS)

AF:

0.188

AC:

967

AN:

5150

South Asian (SAS)

AF:

0.103

AC:

496

AN:

4822

European-Finnish (FIN)

AF:

0.0255

AC:

266

AN:

10442

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0398

AC:

2707

AN:

67976

Other (OTH)

AF:

0.0365

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

285

569

854

1138

1423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0456

Hom.:

722

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Benign

0.14

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

REVEL

Benign

0.056

Sift

Benign

0.068

Sift4G

Benign

0.099

Polyphen

0.60

Vest4

0.23

MPC

0.056

ClinPred

0.012

GERP RS

3.3

PromoterAI

-0.13

Neutral

(source)

Varity_R

0.11

gMVP

0.27

Mutation Taster

=95/5

polymorphism (auto)

(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

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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