rs5749286

Variant names:

• chr22-31504373-C-A
• rs5749286
• NM_001007467.3:c.-30-3882C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

DRG1 Gene-Disease associations (from GenCC):

• Tan-Almurshedi syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFI1	NM_001007467.3	MANE Select	c.-30-3882C>A		intron	N/A	NP_001007468.1	A8K8P3-1
	SFI1	NM_014775.4		c.-30-3882C>A		intron	N/A	NP_055590.2	A8K8P3-2
	SFI1	NM_001258325.1		c.-30-3882C>A		intron	N/A	NP_001245254.1	A8K8P3-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFI1	ENST00000400288.7	TSL:2 MANE Select	c.-30-3882C>A		intron	N/A	ENSP00000383145.2	A8K8P3-1
	SFI1	ENST00000432498.5	TSL:1	c.-30-3882C>A		intron	N/A	ENSP00000402679.1	A8K8P3-2
	SFI1	ENST00000400289.5	TSL:1	c.-26-3886C>A		intron	N/A	ENSP00000383146.1	A8K8P3-3

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

African (AFR) AF: 0.0556 AC: 2306 AN: 41490

American (AMR) AF: 0.257 AC: 3916 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2252 AN: 5160

South Asian (SAS) AF: 0.213 AC: 1029 AN: 4824

European-Finnish (FIN) AF: 0.329 AC: 3476 AN: 10550

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18737 AN: 67966

Other (OTH) AF: 0.197 AC: 415 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.70
PhyloP100		-1.3
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: rs5749286; hg19: chr22-31900359;