chr18-12550748-T-C

Variant names:

• chr18-12550748-T-C
• rs1940973
• NM_001128626.2:c.373-3844A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128626.2. 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
	SPIRE1	NM_001128626.2	MANE Select	c.373-3844A>G		intron	N/A	NP_001122098.1
	SPIRE1	NM_020148.3		c.373-3844A>G		intron	N/A	NP_064533.3
	SPIRE1	NM_001394323.1		c.49-3844A>G		intron	N/A	NP_001381252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIRE1	ENST00000409402.9	TSL:1 MANE Select	c.373-3844A>G		intron	N/A	ENSP00000387266.3
	SPIRE1	ENST00000410092.7	TSL:1	c.373-3844A>G		intron	N/A	ENSP00000387226.3
	SPIRE1	ENST00000440472.6	TSL:1	n.-105-3844A>G		intron	N/A	ENSP00000404752.1

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

African (AFR) AF: 0.0381 AC: 1584 AN: 41532

American (AMR) AF: 0.101 AC: 1535 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3470

East Asian (EAS) AF: 0.0128 AC: 66 AN: 5174

South Asian (SAS) AF: 0.129 AC: 623 AN: 4816

European-Finnish (FIN) AF: 0.0450 AC: 476 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7229 AN: 68008

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.101 Hom.: 2239

Bravo AF: 0.0823

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.79
PhyloP100		0.49
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: rs1940973; hg19: chr18-12550747;