4-53014978-C-T

Variant summary

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

The NM_152540.4(SCFD2):c.1562-94108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,028 control chromosomes in the GnomAD database, including 5,328 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 0.26 (5328 hom., cov: 32)
• Consequence: SCFD2 NM_152540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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 = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCFD2	NM_152540.4	c.1562-94108G>A		intron_variant		ENST00000401642.8
SCFD2	XM_017007786.3	c.*2334G>A		3_prime_UTR_variant	6/6
SCFD2	XM_017007787.3	c.*613G>A		3_prime_UTR_variant	7/7
SCFD2	XM_047449646.1	c.*1075G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCFD2	ENST00000401642.8	c.1562-94108G>A		intron_variant		1	NM_152540.4	P1
SCFD2	ENST00000388940.8	c.1562-94108G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39119 AN: 151910 Hom.: 5325 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.257 AC: 39134 AN: 152028 Hom.: 5328 Cov.: 32 AF XY: 0.253 AC XY: 18831 AN XY: 74318

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.252

Alfa AF: 0.155 Hom.: 318

Bravo AF: 0.248

Asia WGS AF: 0.262 AC: 912 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	0.81
Dann	Benign	0.65

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: rs922904; hg19: chr4-53881145;