8-47394989-G-A

Position:

• chr8-47394989-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001080394.4(SPIDR):​c.526-1387G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 152,280 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 Likely benign (★).

• Frequency: Genomes: 𝑓 0.0015 (0 hom., cov: 32)
• Consequence: SPIDR NM_001080394.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.947

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-47394989-G-A is Benign according to our data. Variant chr8-47394989-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052088.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIDR	NM_001080394.4	c.526-1387G>A		intron_variant		ENST00000297423.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIDR	ENST00000297423.9	c.526-1387G>A		intron_variant		1	NM_001080394.4	P1

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 236 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.000959

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

GnomAD4 genome AF: 0.00154 AC: 235 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.00142 AC XY: 106 AN XY: 74462

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00228 Hom.: 1

Bravo AF: 0.00171

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SPIDR-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs186376230; hg19: chr8-48307549;