Variant chr8-47407967-G-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_001080394.4(SPIDR):c.877+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,515,184 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 55 hom. )

Consequence

SPIDR
NM_001080394.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002753

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0560

Variant links:

Genes affected

SPIDR (HGNC:28971): (scaffold protein involved in DNA repair) Involved in several processes, including cellular response to camptothecin; cellular response to hydroxyurea; and regulation of double-strand break repair. Located in nuclear chromosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPIDR 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=-0.68).

BP6

Variant 8-47407967-G-A is Benign according to our data. Variant chr8-47407967-G-A is described in ClinVar as [Benign]. Clinvar id is 769340.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	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIDR	NM_001080394.4 linkuse as main transcript	c.877+6G>A		splice_donor_region_variant, intron_variant		ENST00000297423.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIDR	ENST00000297423.9 linkuse as main transcript	c.877+6G>A		splice_donor_region_variant, intron_variant		1	NM_001080394.4	P1	Q14159-1

Frequencies

GnomAD3 genomes

AF:

0.00582

AC:

881

AN:

151358

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.00466

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00522

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00803

Gnomad OTH

AF:

0.00682

GnomAD3 exomes

AF:

0.00685

AC:

1579

AN:

230534

Hom.:

AF XY:

0.00681

AC XY:

855

AN XY:

125528

show subpopulations

Gnomad AFR exome

AF:

0.000746

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00488

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.00786

Gnomad OTH exome

AF:

0.00900

GnomAD4 exome

AF:

0.00689

AC:

9398

AN:

1363708

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

4665

AN XY:

680630

show subpopulations

Gnomad4 AFR exome

AF:

0.000903

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.00414

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00489

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.00714

Gnomad4 OTH exome

AF:

0.00655

GnomAD4 genome

AF:

0.00581

AC:

880

AN:

151476

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

415

AN XY:

73946

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00465

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00501

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.00803

Gnomad4 OTH

AF:

0.00675

Alfa

AF:

0.00590

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	SPIDR: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
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

-0.68

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.0020

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