rs12967284

Positions:

• chr18-12532099-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128626.2(SPIRE1):​c.729+3377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,034 control chromosomes in the GnomAD database, including 9,186 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 0.34 (9186 hom., cov: 32)
• Consequence: SPIRE1 NM_001128626.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

Genes affected

SPIRE1 (HGNC:30622): (spire type actin nucleation factor 1) Spire proteins, such as SPIRE1, are highly conserved between species. They belong to the family of Wiskott-Aldrich homology region-2 (WH2) proteins, which are involved in actin organization (Kerkhoff et al., 2001 [PubMed 11747823]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIRE1	NM_001128626.2	c.729+3377G>A		intron_variant		ENST00000409402.9	NP_001122098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIRE1	ENST00000409402.9	c.729+3377G>A		intron_variant		1	NM_001128626.2	ENSP00000387266	A2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51881 AN: 151916 Hom.: 9180 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.342 AC: 51930 AN: 152034 Hom.: 9186 Cov.: 32 AF XY: 0.343 AC XY: 25450 AN XY: 74304

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.385

Alfa AF: 0.361 Hom.: 9673

Bravo AF: 0.342

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.41

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: rs12967284; hg19: chr18-12532098;