rs5749286

Positions:

• chr22-31504373-C-A
• chr22-31504373-C-T

Variant summary

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

The NM_001007467.3(SFI1):​c.-30-3882C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,018 control chromosomes in the GnomAD database, including 4,599 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 0.22 (4599 hom., cov: 31)
• Consequence: SFI1 NM_001007467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

SFI1 (HGNC:29064): (SFI1 centrin binding protein) Enables phosphatase binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DRG1 (HGNC:3029): (developmentally regulated GTP binding protein 1) Enables several functions, including GTPase activity; identical protein binding activity; and potassium ion binding activity. Involved in positive regulation of microtubule polymerization and regulation of mitotic spindle assembly. Located in cytosol and nuclear body. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFI1	NM_001007467.3	c.-30-3882C>A		intron_variant		ENST00000400288.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFI1	ENST00000400288.7	c.-30-3882C>A		intron_variant		2	NM_001007467.3	A2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33050 AN: 151900 Hom.: 4597 Cov.: 31

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.217 AC: 33058 AN: 152018 Hom.: 4599 Cov.: 31 AF XY: 0.221 AC XY: 16448 AN XY: 74308

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.197

Alfa AF: 0.193 Hom.: 720

Bravo AF: 0.207

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.70

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: rs5749286; hg19: chr22-31900359;