rs11663391

Variant names:

• chr18-12516769-C-A
• rs11663391
• NM_001128626.2:c.730-4238G>T

Variant summary

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

The NM_001128626.2(SPIRE1):​c.730-4238G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 151,950 control chromosomes in the GnomAD database, including 9,287 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 (9287 hom., cov: 32)
• Consequence: SPIRE1 NM_001128626.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIRE1	NM_001128626.2	c.730-4238G>T		intron_variant	Intron 4 of 16	ENST00000409402.9	NP_001122098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIRE1	ENST00000409402.9	c.730-4238G>T		intron_variant	Intron 4 of 16	1	NM_001128626.2	ENSP00000387266.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52093 AN: 151832 Hom.: 9276 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.343 AC: 52153 AN: 151950 Hom.: 9287 Cov.: 32 AF XY: 0.343 AC XY: 25501 AN XY: 74252

African (AFR) AF: 0.308 AC: 12753 AN: 41402

American (AMR) AF: 0.352 AC: 5374 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2094 AN: 5166

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4810

European-Finnish (FIN) AF: 0.262 AC: 2765 AN: 10554

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23603 AN: 67952

Other (OTH) AF: 0.386 AC: 813 AN: 2108

Alfa AF: 0.351 Hom.: 8178

Bravo AF: 0.345

Asia WGS AF: 0.475 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.27
PhyloP100		-1.7
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: rs11663391; hg19: chr18-12516768;