Variant chr4-112644730-AAAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PM4_SupportingBP6_Very_StrongBS2

The NM_016648.4(LARP7):c.65_67del(p.Glu22del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,611,350 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0046 ( 21 hom. )

Consequence

LARP7
NM_016648.4 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.45

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 -11 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_016648.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 4-112644730-AAAG-A is Benign according to our data. Variant chr4-112644730-AAAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 777974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-112644730-AAAG-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP7	NM_016648.4 linkuse as main transcript	c.65_67del	p.Glu22del	inframe_deletion	2/13	ENST00000344442.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP7	ENST00000344442.10 linkuse as main transcript	c.65_67del	p.Glu22del	inframe_deletion	2/13	2	NM_016648.4	P4	Q4G0J3-1

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

442

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00539

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00273

AC:

678

AN:

248796

Hom.:

AF XY:

0.00296

AC XY:

400

AN XY:

134988

show subpopulations

Gnomad AFR exome

AF:

0.000970

Gnomad AMR exome

AF:

0.000875

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.000649

Gnomad NFE exome

AF:

0.00475

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00457

AC:

6665

AN:

1459336

Hom.:

AF XY:

0.00440

AC XY:

3194

AN XY:

726050

show subpopulations

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.000829

Gnomad4 ASJ exome

AF:

0.000921

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00172

Gnomad4 FIN exome

AF:

0.000600

Gnomad4 NFE exome

AF:

0.00555

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00291

AC:

442

AN:

152014

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

193

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.00539

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00287

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	LARP7: PM4:Supporting, BS2 -

LARP7-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 10, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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