18-12606464-G-T

Variant names:

• chr18-12606464-G-T
• rs9959145
• NM_001128626.2:c.372+28598C>A

Variant summary

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

The NM_001128626.2(SPIRE1):​c.372+28598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,046 control chromosomes in the GnomAD database, including 637 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 0.080 (637 hom., cov: 32)
• Consequence: SPIRE1 NM_001128626.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 12 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIRE1	NM_001128626.2	c.372+28598C>A		intron_variant	Intron 2 of 16	ENST00000409402.9	NP_001122098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIRE1	ENST00000409402.9	c.372+28598C>A		intron_variant	Intron 2 of 16	1	NM_001128626.2	ENSP00000387266.3

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12220 AN: 151936 Hom.: 637 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0804 AC: 12225 AN: 152046 Hom.: 637 Cov.: 32 AF XY: 0.0792 AC XY: 5883 AN XY: 74310

African (AFR) AF: 0.0366 AC: 1519 AN: 41500

American (AMR) AF: 0.0979 AC: 1494 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5188

South Asian (SAS) AF: 0.130 AC: 625 AN: 4810

European-Finnish (FIN) AF: 0.0445 AC: 468 AN: 10526

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7228 AN: 67970

Other (OTH) AF: 0.115 AC: 243 AN: 2114

Alfa AF: 0.0945 Hom.: 1740

Bravo AF: 0.0817

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.53
PhyloP100		2.3
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: rs9959145; hg19: chr18-12606463;