Genetic Variant CRISPLD1:p.Pro130Leu (chr8-75012901-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001286777.2(CRISPLD1):c.-54C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000103 in 1,610,886 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 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

CRISPLD1
NM_001286777.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

Publications

3 publications found

Variant links:

Genes affected

CRISPLD1 (HGNC:18206): (cysteine rich secretory protein LCCL domain containing 1) Involved in face morphogenesis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CRISPLD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14029124).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286777.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRISPLD1	NM_031461.6	MANE Select	c.389C>T	p.Pro130Leu	missense	Exon 4 of 15	NP_113649.1	Q9H336-1
CRISPLD1	NM_001286777.2		c.-54C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	NP_001273706.1	Q9H336-2
CRISPLD1	NM_001286778.2		c.-176C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	NP_001273707.1	B7Z8V9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRISPLD1	ENST00000262207.9	TSL:1 MANE Select	c.389C>T	p.Pro130Leu	missense	Exon 4 of 15	ENSP00000262207.4	Q9H336-1
CRISPLD1	ENST00000517786.1	TSL:2	c.-54C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	ENSP00000429746.1	Q9H336-2
CRISPLD1	ENST00000523524.5	TSL:2	c.-176C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	ENSP00000430105.1	B7Z8V9

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000801

AC:

AN:

249620

AF XY:

0.0000667

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000857

AC:

125

AN:

1458870

Hom.:

Cov.:

AF XY:

0.0000772

AC XY:

AN XY:

725576

show subpopulations

African (AFR)

AF:

0.000809

AC:

AN:

33356

American (AMR)

AF:

0.0000225

AC:

AN:

44392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

85876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000829

AC:

AN:

1110316

Other (OTH)

AF:

0.0000664

AC:

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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:

0.000270

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000844

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.000134

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

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

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

0.016

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

M_CAP

Benign

0.019

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

4.9

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.13

Sift

Benign

0.098

Sift4G

Benign

0.11

Polyphen

0.055

Vest4

0.48

MVP

0.54

MPC

0.21

ClinPred

0.076

GERP RS

5.2

Varity_R

0.26

gMVP

0.85

Mutation Taster

=235/65

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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