16-84849496-C-T

Position:

• chr16-84849496-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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 -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/exons	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.471C>T	p.Pro157Pro	synonymous_variant	4/15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.471C>T	p.Pro157Pro	synonymous_variant	5/16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.471C>T	p.Pro157Pro	synonymous_variant	4/15	1	NM_031476.4	ENSP00000262424.5

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93751 AN: 152018 Hom.: 31143 Cov.: 33

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

GnomAD3 exomes AF: 0.695 AC: 174692 AN: 251260 Hom.: 62196 AF XY: 0.707 AC XY: 95989 AN XY: 135804

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 SAS exome AF: 0.754

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.: 52 AF XY: 0.729 AC XY: 530105 AN XY: 727090

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.712

GnomAD4 genome AF: 0.616 AC: 93779 AN: 152136 Hom.: 31149 Cov.: 33 AF XY: 0.619 AC XY: 46001 AN XY: 74370

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.641

Alfa AF: 0.705 Hom.: 53812

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	11
DANN	Benign	0.72

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: rs8061351; hg19: chr16-84883102; COSMIC: COSV52278058; COSMIC: COSV52278058;