chr8-75016574-A-T

Variant names:

• chr8-75016574-A-T
• rs1813031270
• NM_031461.6:c.737A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031461.6(CRISPLD1):​c.737A>T​(p.Asp246Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CRISPLD1 NM_031461.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61
• Publications: 0 publications found

Genes affected

CRISPLD1 (HGNC:18206): (cysteine rich secretory protein LCCL domain containing 1) Involved in face morphogenesis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24774012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031461.6. 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
	CRISPLD1	NM_031461.6	MANE Select	c.737A>T	p.Asp246Val	missense	Exon 7 of 15	NP_113649.1	Q9H336-1
	CRISPLD1	NM_001286777.2		c.179A>T	p.Asp60Val	missense	Exon 5 of 13	NP_001273706.1	Q9H336-2
	CRISPLD1	NM_001286778.2		c.173A>T	p.Asp58Val	missense	Exon 6 of 14	NP_001273707.1	B7Z8V9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRISPLD1	ENST00000262207.9	TSL:1 MANE Select	c.737A>T	p.Asp246Val	missense	Exon 7 of 15	ENSP00000262207.4	Q9H336-1
	CRISPLD1	ENST00000959492.1		c.737A>T	p.Asp246Val	missense	Exon 7 of 15	ENSP00000629551.1
	CRISPLD1	ENST00000916000.1		c.737A>T	p.Asp246Val	missense	Exon 7 of 15	ENSP00000586059.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.6
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.59	N
REVEL	Uncertain	0.30
Sift	Benign	0.036	D
Sift4G	Uncertain	0.022	D
Polyphen		0.090	B
Vest4		0.38
MutPred		0.28		Loss of solvent accessibility (P = 0.0544)
MVP		0.88
MPC		0.29
ClinPred		0.87	D
GERP RS		3.7
Varity_R		0.14
gMVP		0.75
Mutation Taster		=89/11	polymorphism

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: rs1813031270; hg19: chr8-75928809;