18-12550748-T-C

Position:

• chr18-12550748-T-C

Variant summary

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

The NM_001128626.2(SPIRE1):​c.373-3844A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 152,158 control chromosomes in the GnomAD database, including 646 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 0.081 (646 hom., cov: 32)
• Consequence: SPIRE1 NM_001128626.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIRE1	NM_001128626.2	c.373-3844A>G		intron_variant		ENST00000409402.9	NP_001122098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIRE1	ENST00000409402.9	c.373-3844A>G		intron_variant		1	NM_001128626.2	ENSP00000387266.3

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12336 AN: 152040 Hom.: 646 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.0811 AC: 12342 AN: 152158 Hom.: 646 Cov.: 32 AF XY: 0.0799 AC XY: 5946 AN XY: 74394

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.118

Alfa AF: 0.106 Hom.: 1724

Bravo AF: 0.0823

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.79

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: rs1940973; hg19: chr18-12550747;