8-47348995-C-G

Variant names:

• chr8-47348995-C-G
• rs10108778
• NM_001080394.4:c.526-47381C>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.526-47381C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,118 control chromosomes in the GnomAD database, including 40,972 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 0.73 (40972 hom., cov: 33)
• Consequence: SPIDR NM_001080394.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 0 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):

• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 9

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIDR	NM_001080394.4	MANE Select	c.526-47381C>G		intron	N/A	NP_001073863.1
	SPIDR	NM_001352931.1		c.526-47381C>G		intron	N/A	NP_001339860.1
	SPIDR	NM_001282919.1		c.346-47381C>G		intron	N/A	NP_001269848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIDR	ENST00000297423.9	TSL:1 MANE Select	c.526-47381C>G		intron	N/A	ENSP00000297423.4
	SPIDR	ENST00000524126.5	TSL:1	n.525+54965C>G		intron	N/A	ENSP00000430941.1
	SPIDR	ENST00000518074.5	TSL:2	c.346-47381C>G		intron	N/A	ENSP00000429487.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111353 AN: 152000 Hom.: 40934 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.733 AC: 111448 AN: 152118 Hom.: 40972 Cov.: 33 AF XY: 0.729 AC XY: 54203 AN XY: 74358

African (AFR) AF: 0.720 AC: 29864 AN: 41492

American (AMR) AF: 0.810 AC: 12380 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2462 AN: 3470

East Asian (EAS) AF: 0.814 AC: 4211 AN: 5172

South Asian (SAS) AF: 0.585 AC: 2821 AN: 4820

European-Finnish (FIN) AF: 0.691 AC: 7288 AN: 10550

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.735 AC: 49985 AN: 68010

Other (OTH) AF: 0.753 AC: 1589 AN: 2110

Alfa AF: 0.730 Hom.: 5013

Bravo AF: 0.744

Asia WGS AF: 0.696 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.15
PhyloP100		-2.1
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: rs10108778; hg19: chr8-48261562;