rs34944112

Positions:

• chr19-50423308-C-T

Variant summary

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

The NM_003121.5(SPIB):​c.339+271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 505,606 control chromosomes in the GnomAD database, including 3,144 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 0.11 (922 hom., cov: 31)
  • Exomes 𝑓: 0.11 (2222 hom.)
• Consequence: SPIB NM_003121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIB	NM_003121.5	c.339+271C>T		intron_variant		ENST00000595883.6	NP_003112.2
SPIB	NM_001243998.2	c.67-297C>T		intron_variant			NP_001230927.1
SPIB	NM_001243999.2	c.339+271C>T		intron_variant			NP_001230928.1
SPIB	NM_001244000.2	c.281+271C>T		intron_variant			NP_001230929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIB	ENST00000595883.6	c.339+271C>T		intron_variant		1	NM_003121.5	ENSP00000471921	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16617 AN: 151992 Hom.: 920 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.110 AC: 38976 AN: 353494 Hom.: 2222 AF XY: 0.111 AC XY: 20314 AN XY: 182366

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0739

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.109 AC: 16621 AN: 152112 Hom.: 922 Cov.: 31 AF XY: 0.108 AC XY: 8005 AN XY: 74342

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0642

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.119

Alfa AF: 0.114 Hom.: 226

Bravo AF: 0.114

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.68

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: rs34944112; hg19: chr19-50926565;