4-53265372-G-A

Position:

• chr4-53265372-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.1311+8454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,886 control chromosomes in the GnomAD database, including 18,040 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 0.47 (18040 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SCFD2 NM_152540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCFD2	NM_152540.4	c.1311+8454C>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.1311+8454C>T		intron_variant		1	NM_152540.4	ENSP00000384182	P1
SCFD2	ENST00000388940.8	c.1311+8454C>T		intron_variant		2		ENSP00000373592

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71421 AN: 151768 Hom.: 18035 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.470 AC: 71454 AN: 151886 Hom.: 18040 Cov.: 32 AF XY: 0.474 AC XY: 35165 AN XY: 74226

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.481

Alfa AF: 0.523 Hom.: 4688

Bravo AF: 0.462

Asia WGS AF: 0.308 AC: 1071 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.43

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: rs751266; hg19: chr4-54131539;