rs10507873

chr13-77643556-G-A

Variant summary

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

The NM_144777.3(SCEL):c.2051-702G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,928 control chromosomes in the GnomAD database, including 2,416 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 0.17 (2416 hom., cov: 32)
• Consequence: SCEL NM_144777.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

Genes affected

SCEL (HGNC:10573): (sciellin) The protein encoded by this gene is a precursor to the cornified envelope of terminally differentiated keratinocytes. This protein localizes to the periphery of cells and may function in the assembly or regulation of proteins in the cornified envelope. Transcript variants encoding different isoforms exist. A transcript variant utilizing an alternative polyA signal has been described in the literature, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCEL	NM_144777.3	c.2051-702G>A		intron_variant		ENST00000349847.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCEL	ENST00000349847.4	c.2051-702G>A		intron_variant		1	NM_144777.3	P2
SCEL	ENST00000377246.7	c.1991-702G>A		intron_variant		1		A2
SCEL	ENST00000535157.5	c.1925-702G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25127 AN: 151810 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.166 AC: 25149 AN: 151928 Hom.: 2416 Cov.: 32 AF XY: 0.169 AC XY: 12536 AN XY: 74262

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.155

Alfa AF: 0.159 Hom.: 4248

Bravo AF: 0.159

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	9.2
Dann	Benign	0.79

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: rs10507873; hg19: chr13-78217691;