rs12051468

Positions:

• chr16-84845858-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031476.4(CRISPLD2):​c.313A>G​(p.Ser105Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,612,638 control chromosomes in the GnomAD database, including 146,223 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (12631 hom., cov: 32)
  • Exomes 𝑓: 0.42 (133592 hom.)
• Consequence: CRISPLD2 NM_031476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010897517).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.313A>G	p.Ser105Gly	missense_variant	3/15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.313A>G	p.Ser105Gly	missense_variant	4/16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.313A>G	p.Ser105Gly	missense_variant	3/15	1	NM_031476.4	ENSP00000262424.5

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61451 AN: 151986 Hom.: 12619 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.390 AC: 97851 AN: 250646 Hom.: 20077 AF XY: 0.400 AC XY: 54149 AN XY: 135506

Gnomad AFR exome AF: 0.400

Gnomad AMR exome AF: 0.284

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.451

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.424 AC: 618936 AN: 1460534 Hom.: 133592 Cov.: 36 AF XY: 0.425 AC XY: 308911 AN XY: 726614

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.404 AC: 61500 AN: 152104 Hom.: 12631 Cov.: 32 AF XY: 0.400 AC XY: 29753 AN XY: 74352

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.404

Alfa AF: 0.424 Hom.: 25049

Bravo AF: 0.395

TwinsUK AF: 0.448 AC: 1660

ALSPAC AF: 0.435 AC: 1678

ESP6500AA AF: 0.400 AC: 1760

ESP6500EA AF: 0.427 AC: 3675

ExAC AF: 0.397 AC: 48251

Asia WGS AF: 0.314 AC: 1093 AN: 3478

EpiCase AF: 0.437

EpiControl AF: 0.438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.51
DEOGEN2	Benign	0.0056	T;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.57	T;T;T;T
MetaRNN	Benign	0.0011	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.43	N;.;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.39	T;T;T;T
Sift4G	Benign	0.56	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.052
MPC		0.048
ClinPred		0.0044	T
GERP RS		-5.8
Varity_R		0.051
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs12051468; hg19: chr16-84879464; COSMIC: COSV52281443; COSMIC: COSV52281443;