4-52890833-G-A

Variant names:

• chr4-52890833-G-A
• rs2898681
• NM_152540.4:c.1843-4967C>T

Variant summary

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

The NM_152540.4(SCFD2):​c.1843-4967C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,926 control chromosomes in the GnomAD database, including 3,269 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 0.21 (3269 hom., cov: 32)
• Consequence: SCFD2 NM_152540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 14 publications found

Genes affected

SCFD2 (HGNC:30676): (sec1 family domain containing 2) Predicted to enable syntaxin binding activity. Predicted to be involved in intracellular protein transport and vesicle docking involved in exocytosis. Predicted to be active in plasma membrane and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152540.4. 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
	SCFD2	NM_152540.4	MANE Select	c.1843-4967C>T		intron	N/A	NP_689753.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD2	ENST00000401642.8	TSL:1 MANE Select	c.1843-4967C>T		intron	N/A	ENSP00000384182.3
	SCFD2	ENST00000388940.8	TSL:2	c.1708-4967C>T		intron	N/A	ENSP00000373592.4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31135 AN: 151808 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.205 AC: 31168 AN: 151926 Hom.: 3269 Cov.: 32 AF XY: 0.204 AC XY: 15116 AN XY: 74260

African (AFR) AF: 0.211 AC: 8714 AN: 41384

American (AMR) AF: 0.165 AC: 2528 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1386 AN: 5142

South Asian (SAS) AF: 0.192 AC: 924 AN: 4808

European-Finnish (FIN) AF: 0.206 AC: 2180 AN: 10558

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13869 AN: 67966

Other (OTH) AF: 0.205 AC: 431 AN: 2106

Alfa AF: 0.206 Hom.: 11335

Bravo AF: 0.203

Asia WGS AF: 0.255 AC: 887 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	6.2
DANN	Benign	0.64
PhyloP100		0.25
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: rs2898681; hg19: chr4-53757000;