8-74990527-A-G

Variant names:

• chr8-74990527-A-G
• rs7841231
• NM_031461.6:c.258+4282A>G

Variant summary

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

The NM_031461.6(CRISPLD1):​c.258+4282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,628 control chromosomes in the GnomAD database, including 17,248 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 0.44 (17248 hom., cov: 31)
• Consequence: CRISPLD1 NM_031461.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRISPLD1	NM_031461.6	c.258+4282A>G		intron_variant	Intron 2 of 14	ENST00000262207.9	NP_113649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRISPLD1	ENST00000262207.9	c.258+4282A>G		intron_variant	Intron 2 of 14	1	NM_031461.6	ENSP00000262207.4
CRISPLD1	ENST00000520277.1	c.258+4282A>G		intron_variant	Intron 3 of 3	5		ENSP00000430504.1
CRISPLD1	ENST00000519798.1	n.511+4410A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66264 AN: 151510 Hom.: 17198 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.438 AC: 66374 AN: 151628 Hom.: 17248 Cov.: 31 AF XY: 0.435 AC XY: 32202 AN XY: 74060

African (AFR) AF: 0.741 AC: 30619 AN: 41346

American (AMR) AF: 0.295 AC: 4500 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1518 AN: 5124

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4816

European-Finnish (FIN) AF: 0.381 AC: 3976 AN: 10442

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22067 AN: 67874

Other (OTH) AF: 0.406 AC: 855 AN: 2108

Alfa AF: 0.302 Hom.: 1145

Bravo AF: 0.444

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0080
DANN	Benign	0.28
PhyloP100		-2.9
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: rs7841231; hg19: chr8-75902762;