4-112646604-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_016648.4(LARP7):c.320C>T(p.Thr107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,593,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

LARP7
NM_016648.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:7B:1

Conservation

PhyloP100: 2.24

Publications

6 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 links:

MIR302CHG (HGNC:41070): (miR-302/367 cluster host gene)

MIR302CHG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07805437).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000428 (65/151836) while in subpopulation NFE AF = 0.000647 (44/67960). AF 95% confidence interval is 0.000495. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.320C>T	p.Thr107Ile	missense	Exon 4 of 13	NP_057732.2	Q4G0J3-1
LARP7	NM_001370974.1		c.320C>T	p.Thr107Ile	missense	Exon 4 of 13	NP_001357903.1	A0A8Q3SHN7
LARP7	NM_001370975.1		c.320C>T	p.Thr107Ile	missense	Exon 4 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.320C>T	p.Thr107Ile	missense	Exon 4 of 13	ENSP00000344950.5	Q4G0J3-1
LARP7	ENST00000509061.5	TSL:1	c.320C>T	p.Thr107Ile	missense	Exon 6 of 15	ENSP00000422626.2	Q4G0J3-1
LARP7	ENST00000509622.5	TSL:1	n.*79C>T		non_coding_transcript_exon	Exon 4 of 13	ENSP00000422451.1	D6RBH8

Frequencies

GnomAD3 genomes

AF:

0.000428

AC:

AN:

151718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000461

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.000317

AC:

AN:

233580

AF XY:

0.000323

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.000506

Gnomad OTH exome

AF:

0.000702

GnomAD4 exome

AF:

0.000522

AC:

752

AN:

1441618

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

368

AN XY:

716194

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

33036

American (AMR)

AF:

0.000348

AC:

AN:

43098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25746

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39160

South Asian (SAS)

AF:

0.000204

AC:

AN:

83172

European-Finnish (FIN)

AF:

0.0000575

AC:

AN:

52182

Middle Eastern (MID)

AF:

0.00490

AC:

AN:

5106

European-Non Finnish (NFE)

AF:

0.000597

AC:

657

AN:

1100702

Other (OTH)

AF:

0.000505

AC:

AN:

59416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<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:

0.000428

AC:

AN:

151836

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41424

American (AMR)

AF:

0.000460

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10490

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

67960

Other (OTH)

AF:

0.000952

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000539

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000569

AC:

ESP6500EA

AF:

0.000126

AC:

ExAC

AF:

0.000340

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Microcephalic primordial dwarfism, Alazami type (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.11

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.83

M_CAP

Benign

0.0096

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

PhyloP100

2.2

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.091

Sift

Benign

0.039

Sift4G

Benign

0.067

Polyphen

0.58

Vest4

0.35

MVP

0.61

MPC

0.064

ClinPred

0.059

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.47

Mutation Taster

=43/57

disease causing

(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