Genetic Variant CRISPLD2:p.Pro157Pro (chr16-84849496-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_031476.4(CRISPLD2):c.471C>T(p.Pro157Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,613,702 control chromosomes in the GnomAD database, including 420,683 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 31149 hom., cov: 33)

Exomes 𝑓: 0.73 ( 389534 hom. )

Consequence

CRISPLD2
NM_031476.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

27 publications found

Variant links:

Genes affected

CRISPLD2 (HGNC:25248): (cysteine rich secretory protein LCCL domain containing 2) Predicted to enable glycosaminoglycan binding activity. Involved in face morphogenesis. Located in transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

CRISPLD2 links:

ENSG00000285848 (HGNC:):

ENSG00000285848 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=-0.098 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD2	NM_031476.4 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 4 of 15	ENST00000262424.10	NP_113664.1	Q9H0B8-1A0A140VK80
CRISPLD2	XM_005256190.2 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 5 of 16		XP_005256247.1	Q9H0B8-1A0A140VK80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10 link	c.471C>T	p.Pro157Pro	synonymous_variant	Exon 4 of 15	1	NM_031476.4	ENSP00000262424.5		Q9H0B8-1

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93751

AN:

152018

Hom.:

31143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.734

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.642

GnomAD2 exomes

AF:

0.695

AC:

174692

AN:

251260

AF XY:

0.707

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.639

Gnomad ASJ exome

AF:

0.730

Gnomad EAS exome

AF:

0.694

Gnomad FIN exome

AF:

0.709

Gnomad NFE exome

AF:

0.742

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.727

AC:

1062095

AN:

1461566

Hom.:

389534

Cov.:

AF XY:

0.729

AC XY:

530105

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.329

AC:

11008

AN:

33470

American (AMR)

AF:

0.641

AC:

28670

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

19181

AN:

26134

East Asian (EAS)

AF:

0.700

AC:

27808

AN:

39700

South Asian (SAS)

AF:

0.759

AC:

65443

AN:

86250

European-Finnish (FIN)

AF:

0.710

AC:

37897

AN:

53396

Middle Eastern (MID)

AF:

0.741

AC:

4259

AN:

5744

European-Non Finnish (NFE)

AF:

0.742

AC:

824808

AN:

1111770

Other (OTH)

AF:

0.712

AC:

43021

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

14191

28381

42572

56762

70953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.616

AC:

93779

AN:

152136

Hom.:

31149

Cov.:

AF XY:

0.619

AC XY:

46001

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.342

AC:

14194

AN:

41484

American (AMR)

AF:

0.652

AC:

9969

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

2546

AN:

3470

East Asian (EAS)

AF:

0.692

AC:

3577

AN:

5172

South Asian (SAS)

AF:

0.744

AC:

3588

AN:

4824

European-Finnish (FIN)

AF:

0.706

AC:

7476

AN:

10590

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50234

AN:

67984

Other (OTH)

AF:

0.641

AC:

1355

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1655

3310

4965

6620

8275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.696

Hom.:

77767

Bravo

AF:

0.597

Asia WGS

AF:

0.668

AC:

2323

AN:

3478

EpiCase

AF:

0.736

EpiControl

AF:

0.736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

-0.098

PromoterAI

0.035

Neutral

(source)

Mutation Taster

=84/16

polymorphism (auto)

(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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16-84849496-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over