Genetic Variant CRLS1:p.Pro21Leu (chr20-6006308-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001323563.2(CRLS1):c.-334C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,322,302 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CRLS1
NM_001323563.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.948

Publications

0 publications found

Variant links:

Genes affected

CRLS1 (HGNC:16148): (cardiolipin synthase 1) This gene encodes a member of the CDP-alcohol phosphatidyltransferase class-I family of proteins. The encoded enzyme catalyzes the synthesis of cardiolipin, a phospholipid component of mitochondrial membranes that is critical for mitochondrial function. [provided by RefSeq, Apr 2016]

CRLS1 links:

ENSG00000286235 (HGNC:):

ENSG00000286235 links:

MCM8-AS1 (HGNC:51230): (MCM8 antisense RNA 1)

MCM8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06162882).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323563.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRLS1	NM_019095.6	MANE Select	c.62C>T	p.Pro21Leu	missense	Exon 1 of 7	NP_061968.1	Q9UJA2-1
CRLS1	NM_001323563.2		c.-334C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001310492.1
CRLS1	NM_001323563.2		c.-334C>T		5_prime_UTR	Exon 1 of 7	NP_001310492.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRLS1	ENST00000378863.9	TSL:1 MANE Select	c.62C>T	p.Pro21Leu	missense	Exon 1 of 7	ENSP00000368140.4	Q9UJA2-1
CRLS1	ENST00000452938.5	TSL:1	c.62C>T	p.Pro21Leu	missense	Exon 1 of 6	ENSP00000416770.1	Q6NTG3
ENSG00000286235	ENST00000652720.1		c.2431-3467C>T		intron	N/A	ENSP00000498784.1	A0A494C100

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.0000640

AC:

AN:

31264

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000835

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1170414

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

568196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24210

American (AMR)

AF:

0.000408

AC:

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17332

East Asian (EAS)

AF:

0.00

AC:

AN:

26308

South Asian (SAS)

AF:

0.00

AC:

AN:

42306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26100

Middle Eastern (MID)

AF:

0.000308

AC:

AN:

3248

European-Non Finnish (NFE)

AF:

0.0000196

AC:

AN:

969058

Other (OTH)

AF:

0.0000212

AC:

AN:

47144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151888

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41512

American (AMR)

AF:

0.000393

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67884

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.4

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.39

M_CAP

Benign

0.040

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.95

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.68

REVEL

Benign

0.050

Sift

Benign

0.091

Sift4G

Uncertain

0.048

Polyphen

0.0

Vest4

0.083

MVP

0.20

MPC

0.11

ClinPred

0.049

GERP RS

-8.3

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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