16-84854704-C-T

Variant names:

• chr16-84854704-C-T
• rs4782675
• NM_031476.4:c.609-25C>T

Variant summary

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

The NM_031476.4(CRISPLD2):​c.609-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,577,338 control chromosomes in the GnomAD database, including 43,121 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 0.21 (3659 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39462 hom.)
• Consequence: CRISPLD2 NM_031476.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 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.609-25C>T		intron	N/A	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.609-25C>T		intron	N/A	ENSP00000262424.5	Q9H0B8-1
	CRISPLD2	ENST00000564567.5	TSL:1	c.609-25C>T		intron	N/A	ENSP00000457655.1	Q9H0B8-2
	CRISPLD2	ENST00000941702.1		c.609-25C>T		intron	N/A	ENSP00000611761.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31880 AN: 151946 Hom.: 3655 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.230 AC: 57289 AN: 249394 AF XY: 0.232

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.518

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.229 AC: 326494 AN: 1425274 Hom.: 39462 Cov.: 26 AF XY: 0.230 AC XY: 163457 AN XY: 711324

African (AFR) AF: 0.162 AC: 5305 AN: 32760

American (AMR) AF: 0.144 AC: 6447 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6872 AN: 25890

East Asian (EAS) AF: 0.478 AC: 18873 AN: 39470

South Asian (SAS) AF: 0.226 AC: 19323 AN: 85524

European-Finnish (FIN) AF: 0.178 AC: 9491 AN: 53388

Middle Eastern (MID) AF: 0.279 AC: 1584 AN: 5676

European-Non Finnish (NFE) AF: 0.227 AC: 244543 AN: 1078824

Other (OTH) AF: 0.238 AC: 14056 AN: 59094

GnomAD4 genome AF: 0.210 AC: 31898 AN: 152064 Hom.: 3659 Cov.: 32 AF XY: 0.208 AC XY: 15433 AN XY: 74360

African (AFR) AF: 0.158 AC: 6547 AN: 41488

American (AMR) AF: 0.174 AC: 2658 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3472

East Asian (EAS) AF: 0.498 AC: 2560 AN: 5142

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4828

European-Finnish (FIN) AF: 0.173 AC: 1832 AN: 10572

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15563 AN: 67964

Other (OTH) AF: 0.211 AC: 446 AN: 2116

Alfa AF: 0.223 Hom.: 2787

Bravo AF: 0.213

Asia WGS AF: 0.320 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.017
DANN	Benign	0.89
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4782675; hg19: chr16-84888310; COSMIC: COSV107276651;