rs2898681

Positions:

• chr4-52890833-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCFD2	NM_152540.4	c.1843-4967C>T		intron_variant		ENST00000401642.8	NP_689753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCFD2	ENST00000401642.8	c.1843-4967C>T		intron_variant		1	NM_152540.4	ENSP00000384182.3
SCFD2	ENST00000388940.8	c.1708-4967C>T		intron_variant		2		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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.205

Alfa AF: 0.207 Hom.: 7650

Bravo AF: 0.203

Asia WGS AF: 0.255 AC: 887 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	6.2
DANN	Benign	0.64

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: rs2898681; hg19: chr4-53757000;