chr15-74848513-G-A

Position:

• chr15-74848513-G-A

Variant summary

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

The NM_005697.5(SCAMP2):​c.734+87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 829,814 control chromosomes in the GnomAD database, including 146,808 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 0.48 (21074 hom., cov: 31)
  • Exomes 𝑓: 0.59 (125734 hom.)
• Consequence: SCAMP2 NM_005697.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

SCAMP2 (HGNC:10564): (secretory carrier membrane protein 2) This gene product belongs to the SCAMP family of proteins which are secretory carrier membrane proteins. They function as carriers to the cell surface in post-golgi recycling pathways. Different family members are highly related products of distinct genes, and are usually expressed together. These findings suggest that the SCAMPs may function at the same site during vesicular transport rather than in separate pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAMP2	NM_005697.5	c.734+87C>T		intron_variant		ENST00000268099.13	NP_005688.2
SCAMP2	NM_001320778.2	c.863+87C>T		intron_variant			NP_001307707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAMP2	ENST00000268099.13	c.734+87C>T		intron_variant		1	NM_005697.5	ENSP00000268099	P1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73594 AN: 151886 Hom.: 21079 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.595 AC: 402977 AN: 677810 Hom.: 125734 Cov.: 9 AF XY: 0.583 AC XY: 206237 AN XY: 353888

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.484 AC: 73595 AN: 152004 Hom.: 21074 Cov.: 31 AF XY: 0.477 AC XY: 35427 AN XY: 74272

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.509

Alfa AF: 0.608 Hom.: 28085

Bravo AF: 0.476

Asia WGS AF: 0.375 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.40

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: rs3765066; hg19: chr15-75140854;