8-142741000-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020427.3(SLURP1):c.*143G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,237,128 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (21 hom.)
• Consequence: SLURP1 NM_020427.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800

Genes affected

SLURP1 (HGNC:18746): (secreted LY6/PLAUR domain containing 1) The protein encoded by this gene is a member of the Ly6/uPAR family but lacks a GPI-anchoring signal sequence. It is thought that this secreted protein contains antitumor activity. Mutations in this gene have been associated with Mal de Meleda, a rare autosomal recessive skin disorder. This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-142741000-C-T is Benign according to our data. Variant chr8-142741000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 362098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00472 (719/152194) while in subpopulation SAS AF= 0.00705 (34/4820). AF 95% confidence interval is 0.00527. There are 3 homozygotes in gnomad4. There are 401 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLURP1	NM_020427.3	c.*143G>A		3_prime_UTR_variant	3/3	ENST00000246515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLURP1	ENST00000246515.2	c.*143G>A		3_prime_UTR_variant	3/3	1	NM_020427.3	P1

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 719 AN: 152076 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000894

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00574

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00505 AC: 5480 AN: 1084934 Hom.: 21 Cov.: 14 AF XY: 0.00524 AC XY: 2871 AN XY: 548024

Gnomad4 AFR exome AF: 0.000425

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00760

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.00480

Gnomad4 OTH exome AF: 0.00462

GnomAD4 genome AF: 0.00472 AC: 719 AN: 152194 Hom.: 3 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74396

Gnomad4 AFR AF: 0.000891

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.00574

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00415 Hom.: 0

Bravo AF: 0.00320

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Acroerythrokeratoderma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.0
Dann	Benign	0.65

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: rs182887603; hg19: chr8-143822418;