4-53014978-C-T

Variant names:

• chr4-53014978-C-T
• rs922904
• NM_152540.4:c.1562-94108G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 = 0.306 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD2	NM_152540.4	MANE Select	c.1562-94108G>A		intron	N/A	NP_689753.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD2	ENST00000401642.8	TSL:1 MANE Select	c.1562-94108G>A		intron	N/A	ENSP00000384182.3	Q8WU76-1
	SCFD2	ENST00000910196.1		c.1594+93884G>A		intron	N/A	ENSP00000580255.1
	SCFD2	ENST00000388940.8	TSL:2	c.1562-94108G>A		intron	N/A	ENSP00000373592.4	Q8WU76-2

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

African (AFR) AF: 0.172 AC: 7114 AN: 41456

American (AMR) AF: 0.232 AC: 3542 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5166

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3094 AN: 10568

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

European-Non Finnish (NFE) AF: 0.310 AC: 21058 AN: 67970

Other (OTH) AF: 0.252 AC: 533 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.65
PhyloP100		-0.29
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: rs922904; hg19: chr4-53881145;