Variant 8-75016712-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_031461.6(CRISPLD1):c.868+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,607,302 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 5 hom., cov: 32)

Exomes 𝑓: 0.010 ( 76 hom. )

Consequence

CRISPLD1
NM_031461.6 splice_region, intron

Scores

Splicing: ADA: 0.0002773

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.601

Variant links:

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]

CRISPLD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 8-75016712-C-A is Benign according to our data. Variant chr8-75016712-C-A is described in ClinVar as [Benign]. Clinvar id is 775087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CRISPLD1	NM_031461.6 linkuse as main transcript	c.868+7C>A	splice_region_variant, intron_variant	ENST00000262207.9	NP_113649.1	Q9H336-1
CRISPLD1	NM_001286777.2 linkuse as main transcript	c.310+7C>A	splice_region_variant, intron_variant		NP_001273706.1	Q9H336-2
CRISPLD1	NM_001286778.2 linkuse as main transcript	c.304+7C>A	splice_region_variant, intron_variant		NP_001273707.1	B7Z8V9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CRISPLD1	ENST00000262207.9 linkuse as main transcript	c.868+7C>A	splice_region_variant, intron_variant	1	NM_031461.6	ENSP00000262207.4	Q9H336-1
CRISPLD1	ENST00000517786.1 linkuse as main transcript	c.310+7C>A	splice_region_variant, intron_variant	2		ENSP00000429746.1	Q9H336-2
CRISPLD1	ENST00000523524.5 linkuse as main transcript	c.304+7C>A	splice_region_variant, intron_variant	2		ENSP00000430105.1	B7Z8V9

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1115

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00676

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00741

AC:

1836

AN:

247728

Hom.:

AF XY:

0.00748

AC XY:

1003

AN XY:

134070

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00545

Gnomad ASJ exome

AF:

0.00836

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000430

Gnomad FIN exome

AF:

0.00511

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.00868

GnomAD4 exome

AF:

0.0102

AC:

14856

AN:

1455132

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7243

AN XY:

723920

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00574

Gnomad4 ASJ exome

AF:

0.00773

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000340

Gnomad4 FIN exome

AF:

0.00552

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00731

AC:

1113

AN:

152170

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.00675

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00472

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00745

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.6

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.044

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over