16-84849496-C-T

Variant names:

• chr16-84849496-C-T
• rs8061351
• NM_031476.4:c.471C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_031476.4(CRISPLD2):​c.471C>T​(p.Pro157Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 1,613,702 control chromosomes in the GnomAD database, including 420,683 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 0.62 (31149 hom., cov: 33)
  • Exomes 𝑓: 0.73 (389534 hom.)
• Consequence: CRISPLD2 NM_031476.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 27 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-0.098 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.733 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.471C>T	p.Pro157Pro	synonymous	Exon 4 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.471C>T	p.Pro157Pro	synonymous	Exon 4 of 15	ENSP00000262424.5	Q9H0B8-1
	CRISPLD2	ENST00000564567.5	TSL:1	c.471C>T	p.Pro157Pro	synonymous	Exon 4 of 13	ENSP00000457655.1	Q9H0B8-2
	CRISPLD2	ENST00000941702.1		c.471C>T	p.Pro157Pro	synonymous	Exon 4 of 15	ENSP00000611761.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93751 AN: 152018 Hom.: 31143 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.642

GnomAD2 exomes AF: 0.695 AC: 174692 AN: 251260 AF XY: 0.707

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.639

Gnomad ASJ exome AF: 0.730

Gnomad EAS exome AF: 0.694

Gnomad FIN exome AF: 0.709

Gnomad NFE exome AF: 0.742

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.727 AC: 1062095 AN: 1461566 Hom.: 389534 Cov.: 52 AF XY: 0.729 AC XY: 530105 AN XY: 727090

African (AFR) AF: 0.329 AC: 11008 AN: 33470

American (AMR) AF: 0.641 AC: 28670 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 19181 AN: 26134

East Asian (EAS) AF: 0.700 AC: 27808 AN: 39700

South Asian (SAS) AF: 0.759 AC: 65443 AN: 86250

European-Finnish (FIN) AF: 0.710 AC: 37897 AN: 53396

Middle Eastern (MID) AF: 0.741 AC: 4259 AN: 5744

European-Non Finnish (NFE) AF: 0.742 AC: 824808 AN: 1111770

Other (OTH) AF: 0.712 AC: 43021 AN: 60382

GnomAD4 genome AF: 0.616 AC: 93779 AN: 152136 Hom.: 31149 Cov.: 33 AF XY: 0.619 AC XY: 46001 AN XY: 74370

African (AFR) AF: 0.342 AC: 14194 AN: 41484

American (AMR) AF: 0.652 AC: 9969 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3577 AN: 5172

South Asian (SAS) AF: 0.744 AC: 3588 AN: 4824

European-Finnish (FIN) AF: 0.706 AC: 7476 AN: 10590

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50234 AN: 67984

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.696 Hom.: 77767

Bravo AF: 0.597

Asia WGS AF: 0.668 AC: 2323 AN: 3478

EpiCase AF: 0.736

EpiControl AF: 0.736

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		-0.098
PromoterAI		0.035	Neutral
Mutation Taster		=84/16	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: rs8061351; hg19: chr16-84883102; COSMIC: COSV52278058; COSMIC: COSV52278058;