rs6821328

Positions:

• chr4-53351332-A-G

Variant summary

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

The NM_152540.4(SCFD2):​c.1007+1266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,008 control chromosomes in the GnomAD database, including 15,975 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 0.43 (15975 hom., cov: 32)
• Consequence: SCFD2 NM_152540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCFD2	NM_152540.4	c.1007+1266T>C		intron_variant		ENST00000401642.8	NP_689753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCFD2	ENST00000401642.8	c.1007+1266T>C		intron_variant		1	NM_152540.4	ENSP00000384182	P1
SCFD2	ENST00000388940.8	c.1007+1266T>C		intron_variant		2		ENSP00000373592

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65491 AN: 151890 Hom.: 15966 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.431 AC: 65522 AN: 152008 Hom.: 15975 Cov.: 32 AF XY: 0.434 AC XY: 32277 AN XY: 74286

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.458

Alfa AF: 0.473 Hom.: 2734

Bravo AF: 0.422

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.1
DANN	Benign	0.88

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: rs6821328; hg19: chr4-54217499;