16-84849391-C-T

Variant names:

• chr16-84849391-C-T
• rs138518275
• NM_031476.4:c.366C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_031476.4(CRISPLD2):​c.366C>T​(p.Arg122Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,082 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: CRISPLD2 NM_031476.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.15

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]

ENSG00000285848 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 16-84849391-C-T is Benign according to our data. Variant chr16-84849391-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049850.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.366C>T	p.Arg122Arg	synonymous_variant	Exon 4 of 15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.366C>T	p.Arg122Arg	synonymous_variant	Exon 5 of 16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.366C>T	p.Arg122Arg	synonymous_variant	Exon 4 of 15	1	NM_031476.4	ENSP00000262424.5

Frequencies

GnomAD3 genomes AF: 0.000985 AC: 150 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000917 AC: 230 AN: 250814 Hom.: 0 AF XY: 0.000915 AC XY: 124 AN XY: 135518

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.00218

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.00111 AC: 1620 AN: 1460736 Hom.: 3 Cov.: 42 AF XY: 0.00115 AC XY: 837 AN XY: 726506

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.00257

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000711 AC XY: 53 AN XY: 74502

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00178

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.000756

EpiCase AF: 0.00185

EpiControl AF: 0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CRISPLD2-related disorder Benign:1

Jul 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.8
DANN	Benign	0.67

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: rs138518275; hg19: chr16-84882997;