19-50423748-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003121.5(SPIB):c.483C>T(p.Ser161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,607,342 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (6 hom.)
• Consequence: SPIB NM_003121.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.07

Genes affected

SPIB (HGNC:11242): (Spi-B transcription factor) The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5'-GAGGAA-3') and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 19-50423748-C-T is Benign according to our data. Variant chr19-50423748-C-T is described in ClinVar as [Benign]. Clinvar id is 784719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-6.07 with no splicing effect.
• BS2: High AC in GnomAd at 217 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIB	NM_003121.5	c.483C>T	p.Ser161=	synonymous_variant	5/6	ENST00000595883.6
SPIB	NM_001244000.2	c.390C>T	p.Ser130=	synonymous_variant	5/6
SPIB	NM_001243999.2	c.483C>T	p.Ser161=	synonymous_variant	5/6
SPIB	NM_001243998.2	c.210C>T	p.Ser70=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIB	ENST00000595883.6	c.483C>T	p.Ser161=	synonymous_variant	5/6	1	NM_003121.5	P1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00116 AC: 269 AN: 232424 Hom.: 0 AF XY: 0.00115 AC XY: 145 AN XY: 126356

Gnomad AFR exome AF: 0.000687

Gnomad AMR exome AF: 0.000457

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000573

Gnomad SAS exome AF: 0.0000686

Gnomad FIN exome AF: 0.000406

Gnomad NFE exome AF: 0.00221

Gnomad OTH exome AF: 0.000703

GnomAD4 exome AF: 0.00218 AC: 3177 AN: 1455114 Hom.: 6 Cov.: 32 AF XY: 0.00208 AC XY: 1508 AN XY: 723314

Gnomad4 AFR exome AF: 0.000449

Gnomad4 AMR exome AF: 0.000504

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.000380

Gnomad4 NFE exome AF: 0.00273

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00143 AC: 217 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74448

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00229

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00186 Hom.: 1

Bravo AF: 0.00133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.68
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs117090800; hg19: chr19-50927005;