rs1874014

Variant names:

• chr16-84821910-A-C
• rs1874014
• NM_031476.4:c.-75+1777A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031476.4(CRISPLD2):​c.-75+1777A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,058 control chromosomes in the GnomAD database, including 13,800 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 0.42 (13800 hom., cov: 33)
• Consequence: CRISPLD2 NM_031476.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 12 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]

ENSG00000285848 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD2	NM_031476.4	c.-75+1777A>C		intron_variant	Intron 1 of 14	ENST00000262424.10	NP_113664.1
CRISPLD2	XM_005256190.2	c.-334+1777A>C		intron_variant	Intron 1 of 15		XP_005256247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD2	ENST00000262424.10	c.-75+1777A>C		intron_variant	Intron 1 of 14	1	NM_031476.4	ENSP00000262424.5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63944 AN: 151940 Hom.: 13791 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.421 AC: 63972 AN: 152058 Hom.: 13800 Cov.: 33 AF XY: 0.419 AC XY: 31123 AN XY: 74328

African (AFR) AF: 0.502 AC: 20789 AN: 41450

American (AMR) AF: 0.318 AC: 4866 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5164

South Asian (SAS) AF: 0.409 AC: 1973 AN: 4824

European-Finnish (FIN) AF: 0.394 AC: 4166 AN: 10572

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27838 AN: 67968

Other (OTH) AF: 0.435 AC: 918 AN: 2112

Alfa AF: 0.411 Hom.: 36691

Bravo AF: 0.419

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.51
PhyloP100		-0.48
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: rs1874014; hg19: chr16-84855516;