rs6821328

Variant names:

• chr4-53351332-A-G
• rs6821328
• NM_152540.4:c.1007+1266T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.532 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD2	NM_152540.4	MANE Select	c.1007+1266T>C		intron	N/A	NP_689753.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCFD2	ENST00000401642.8	TSL:1 MANE Select	c.1007+1266T>C		intron	N/A	ENSP00000384182.3
	SCFD2	ENST00000388940.8	TSL:2	c.1007+1266T>C		intron	N/A	ENSP00000373592.4

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

African (AFR) AF: 0.204 AC: 8467 AN: 41504

American (AMR) AF: 0.542 AC: 8263 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1562 AN: 5150

South Asian (SAS) AF: 0.287 AC: 1379 AN: 4812

European-Finnish (FIN) AF: 0.593 AC: 6263 AN: 10556

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35908 AN: 67952

Other (OTH) AF: 0.458 AC: 965 AN: 2108

Alfa AF: 0.464 Hom.: 2752

Bravo AF: 0.422

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.1
DANN	Benign	0.88
PhyloP100		-0.54
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: rs6821328; hg19: chr4-54217499;