15-48996530-A-G

Position:

• chr15-48996530-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The ENST00000559471.6(SECISBP2L):​c.2460T>C​(p.Asp820=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,614,122 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (5 hom.)
• Consequence: SECISBP2L ENST00000559471.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00400

Genes affected

SECISBP2L (HGNC:28997): (SECIS binding protein 2 like) Enables RNA binding activity. Predicted to be involved in selenocysteine incorporation. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-48996530-A-G is Benign according to our data. Variant chr15-48996530-A-G is described in ClinVar as [Benign]. Clinvar id is 708329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SECISBP2L	NM_001193489.2	c.2460T>C	p.Asp820=	synonymous_variant	17/18	ENST00000559471.6	NP_001180418.1
SECISBP2L	NM_014701.4	c.2325T>C	p.Asp775=	synonymous_variant	16/17		NP_055516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SECISBP2L	ENST00000559471.6	c.2460T>C	p.Asp820=	synonymous_variant	17/18	1	NM_001193489.2	ENSP00000453854	P4
SECISBP2L	ENST00000261847.7	c.2325T>C	p.Asp775=	synonymous_variant	16/17	1		ENSP00000261847	A1
SECISBP2L	ENST00000380927.6	c.1746T>C	p.Asp582=	synonymous_variant	17/17	1		ENSP00000370314
SECISBP2L	ENST00000561428.1			upstream_gene_variant		3		ENSP00000454144

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00137 AC: 345 AN: 251352 Hom.: 0 AF XY: 0.00151 AC XY: 205 AN XY: 135838

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00240

Gnomad NFE exome AF: 0.00196

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00192 AC: 2811 AN: 1461836 Hom.: 5 Cov.: 31 AF XY: 0.00188 AC XY: 1367 AN XY: 727218

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000452

Gnomad4 FIN exome AF: 0.00215

Gnomad4 NFE exome AF: 0.00222

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.00141 AC XY: 105 AN XY: 74462

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.00165

EpiCase AF: 0.00180

EpiControl AF: 0.00284

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.7
DANN	Benign	0.82

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: rs150175110; hg19: chr15-49288727;