16-84889253-C-T

Position:

• chr16-84889253-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031476.4(CRISPLD2):​c.1329C>T​(p.Ala443Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,613,536 control chromosomes in the GnomAD database, including 251,731 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 0.59 (26795 hom., cov: 32)
  • Exomes 𝑓: 0.55 (224936 hom.)
• Consequence: CRISPLD2 NM_031476.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.64

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-4.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.1329C>T	p.Ala443Ala	synonymous_variant	14/15	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.1329C>T	p.Ala443Ala	synonymous_variant	15/16		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.1329C>T	p.Ala443Ala	synonymous_variant	14/15	1	NM_031476.4	ENSP00000262424.5
CRISPLD2	ENST00000567845.5	c.1326C>T	p.Ala442Ala	synonymous_variant	14/15	5		ENSP00000457183.1
CRISPLD2	ENST00000566165.1	n.9C>T		non_coding_transcript_exon_variant	1/3	3		ENSP00000463171.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89238 AN: 151860 Hom.: 26781 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.610

GnomAD3 exomes AF: 0.585 AC: 147121 AN: 251340 Hom.: 44223 AF XY: 0.583 AC XY: 79205 AN XY: 135846

Gnomad AFR exome AF: 0.678

Gnomad AMR exome AF: 0.611

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.861

Gnomad SAS exome AF: 0.636

Gnomad FIN exome AF: 0.459

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.551 AC: 805065 AN: 1461558 Hom.: 224936 Cov.: 49 AF XY: 0.552 AC XY: 401568 AN XY: 727094

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.608

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.588 AC: 89297 AN: 151978 Hom.: 26795 Cov.: 32 AF XY: 0.589 AC XY: 43728 AN XY: 74258

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.611

Alfa AF: 0.554 Hom.: 22027

Bravo AF: 0.606

Asia WGS AF: 0.736 AC: 2556 AN: 3478

EpiCase AF: 0.543

EpiControl AF: 0.548

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.20
DANN	Benign	0.56

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: rs767050; hg19: chr16-84922859; COSMIC: COSV105103283;