8-47439843-A-G

Variant names:

• chr8-47439843-A-G
• rs4873102
• NM_001080394.4:c.878-480A>G

Variant summary

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

The NM_001080394.4(SPIDR):​c.878-480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,048 control chromosomes in the GnomAD database, including 22,647 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 0.50 (22647 hom., cov: 32)
• Consequence: SPIDR NM_001080394.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• ovarian dysgenesis 9

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080394.4. 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
	SPIDR	NM_001080394.4	MANE Select	c.878-480A>G		intron	N/A	NP_001073863.1	Q14159-1
	SPIDR	NM_001352931.1		c.878-480A>G		intron	N/A	NP_001339860.1
	SPIDR	NM_001282919.1		c.698-480A>G		intron	N/A	NP_001269848.1	Q14159-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIDR	ENST00000297423.9	TSL:1 MANE Select	c.878-480A>G		intron	N/A	ENSP00000297423.4	Q14159-1
	SPIDR	ENST00000524126.5	TSL:1	n.526-480A>G		intron	N/A	ENSP00000430941.1	E7EVI9
	SPIDR	ENST00000936264.1		c.878-480A>G		intron	N/A	ENSP00000606323.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76156 AN: 151930 Hom.: 22637 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.501 AC: 76195 AN: 152048 Hom.: 22647 Cov.: 32 AF XY: 0.499 AC XY: 37068 AN XY: 74322

African (AFR) AF: 0.165 AC: 6849 AN: 41474

American (AMR) AF: 0.558 AC: 8528 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1899 AN: 3468

East Asian (EAS) AF: 0.659 AC: 3403 AN: 5160

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4824

European-Finnish (FIN) AF: 0.630 AC: 6642 AN: 10544

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45327 AN: 67982

Other (OTH) AF: 0.536 AC: 1130 AN: 2110

Alfa AF: 0.572 Hom.: 10665

Bravo AF: 0.481

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		0.88
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: rs4873102; hg19: chr8-48352405;