rs765019295

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_015956.3(MRPL4):c.740-13A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 0 hom., cov: 0)

Exomes 𝑓: 0.12 ( 240 hom. )

Failed GnomAD Quality Control

Consequence

MRPL4
NM_015956.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.623

Publications

0 publications found

Variant links:

Genes affected

MRPL4 (HGNC:14276): (mitochondrial ribosomal protein L4) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Sequence analysis identified alternatively spliced variants that encode different protein isoforms. [provided by RefSeq, Jul 2008]

MRPL4 links:

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

LIMASI links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-10259604-A-C is Benign according to our data. Variant chr19-10259604-A-C is described in ClinVar as Benign. ClinVar VariationId is 403106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MRPL4	NM_015956.3 link	c.740-13A>C	intron_variant	Intron 8 of 8	ENST00000253099.11	NP_057040.2	Q9BYD3-1A0A024R7C5
MRPL4	NM_001411149.1 link	c.*98A>C	3_prime_UTR_variant	Exon 9 of 9		NP_001398078.1
MRPL4	NM_146388.2 link	c.*866A>C	3_prime_UTR_variant	Exon 8 of 8		NP_666500.1	Q9BYD3-2
MRPL4	NM_146387.2 link	c.740-13A>C	intron_variant	Intron 9 of 9		NP_666499.1	Q9BYD3-1A0A024R7C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL4	ENST00000253099.11 link	c.740-13A>C		intron_variant	Intron 8 of 8	1	NM_015956.3	ENSP00000253099.5		Q9BYD3-1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

8001

AN:

24390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.167

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.329

GnomAD2 exomes

AF:

0.431

AC:

23374

AN:

54276

AF XY:

0.430

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.462

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.121

AC:

37853

AN:

311844

Hom.:

240

Cov.:

AF XY:

0.137

AC XY:

20729

AN XY:

151840

show subpopulations

African (AFR)

AF:

0.173

AC:

1379

AN:

7974

American (AMR)

AF:

0.446

AC:

4611

AN:

10346

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1402

AN:

4566

East Asian (EAS)

AF:

0.199

AC:

1290

AN:

6498

South Asian (SAS)

AF:

0.340

AC:

6723

AN:

19780

European-Finnish (FIN)

AF:

0.337

AC:

2393

AN:

7104

Middle Eastern (MID)

AF:

0.165

AC:

123

AN:

746

European-Non Finnish (NFE)

AF:

0.0749

AC:

18209

AN:

243196

Other (OTH)

AF:

0.148

AC:

1723

AN:

11634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

1447

2894

4341

5788

7235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<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

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.328

AC:

8002

AN:

24406

Hom.:

Cov.:

AF XY:

0.300

AC XY:

3651

AN XY:

12160

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.302

AC:

2059

AN:

6828

American (AMR)

AF:

0.193

AC:

637

AN:

3294

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

209

AN:

522

East Asian (EAS)

AF:

0.297

AC:

117

AN:

394

South Asian (SAS)

AF:

0.319

AC:

144

AN:

452

European-Finnish (FIN)

AF:

0.207

AC:

406

AN:

1966

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.408

AC:

4278

AN:

10498

Other (OTH)

AF:

0.327

AC:

115

AN:

352

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.351

Heterozygous variant carriers

418

836

1253

1671

2089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00374

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.68

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over