16-84889253-C-T

Variant names:

• chr16-84889253-C-T
• rs767050
• NM_031476.4:c.1329C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

ENSG00000279622 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031476.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD2	NM_031476.4	MANE Select	c.1329C>T	p.Ala443Ala	synonymous	Exon 14 of 15	NP_113664.1	Q9H0B8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD2	ENST00000262424.10	TSL:1 MANE Select	c.1329C>T	p.Ala443Ala	synonymous	Exon 14 of 15	ENSP00000262424.5	Q9H0B8-1
	CRISPLD2	ENST00000941702.1		c.1329C>T	p.Ala443Ala	synonymous	Exon 14 of 15	ENSP00000611761.1
	CRISPLD2	ENST00000941703.1		c.1329C>T	p.Ala443Ala	synonymous	Exon 14 of 15	ENSP00000611762.1

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

GnomAD2 exomes AF: 0.585 AC: 147121 AN: 251340 AF XY: 0.583

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 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

African (AFR) AF: 0.679 AC: 22724 AN: 33468

American (AMR) AF: 0.608 AC: 27161 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 14578 AN: 26132

East Asian (EAS) AF: 0.822 AC: 32608 AN: 39688

South Asian (SAS) AF: 0.631 AC: 54412 AN: 86246

European-Finnish (FIN) AF: 0.467 AC: 24944 AN: 53410

Middle Eastern (MID) AF: 0.625 AC: 3605 AN: 5768

European-Non Finnish (NFE) AF: 0.531 AC: 590383 AN: 1111782

Other (OTH) AF: 0.574 AC: 34650 AN: 60368

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

African (AFR) AF: 0.673 AC: 27893 AN: 41450

American (AMR) AF: 0.598 AC: 9124 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1940 AN: 3466

East Asian (EAS) AF: 0.846 AC: 4357 AN: 5148

South Asian (SAS) AF: 0.654 AC: 3152 AN: 4816

European-Finnish (FIN) AF: 0.460 AC: 4861 AN: 10562

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36051 AN: 67958

Other (OTH) AF: 0.611 AC: 1289 AN: 2110

Alfa AF: 0.558 Hom.: 32881

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.20
DANN	Benign	0.56
PhyloP100		-4.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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