rs751266

Variant names:

• chr4-53265372-G-A
• rs751266
• NM_152540.4:c.1311+8454C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

RNU6-310P (HGNC:47273): (RNA, U6 small nuclear 310, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCFD2	NM_152540.4	c.1311+8454C>T		intron_variant	Intron 4 of 8	ENST00000401642.8	NP_689753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCFD2	ENST00000401642.8	c.1311+8454C>T		intron_variant	Intron 4 of 8	1	NM_152540.4	ENSP00000384182.3
SCFD2	ENST00000388940.8	c.1311+8454C>T		intron_variant	Intron 4 of 7	2		ENSP00000373592.4
RNU6-310P	ENST00000384655.1	n.*89C>T		downstream_gene_variant		6

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

African (AFR) AF: 0.296 AC: 12242 AN: 41404

American (AMR) AF: 0.553 AC: 8451 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2062 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1585 AN: 5178

South Asian (SAS) AF: 0.359 AC: 1725 AN: 4804

European-Finnish (FIN) AF: 0.607 AC: 6372 AN: 10496

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37267 AN: 67956

Other (OTH) AF: 0.481 AC: 1014 AN: 2108

Alfa AF: 0.523 Hom.: 7653

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
PhyloP100		-0.14
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: rs751266; hg19: chr4-54131539;