chr19-50425885-G-A

Position:

• chr19-50425885-G-A

Variant summary

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

The ENST00000595883.6(SPIB):​c.490+2130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,000 control chromosomes in the GnomAD database, including 23,599 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 0.52 (23599 hom., cov: 32)
• Consequence: SPIB ENST00000595883.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIB	NM_003121.5	c.490+2130G>A		intron_variant		ENST00000595883.6	NP_003112.2
SPIB	NM_001243998.2	c.217+2130G>A		intron_variant			NP_001230927.1
SPIB	NM_001243999.2	c.486+2134G>A		intron_variant			NP_001230928.1
SPIB	NM_001244000.2	c.397+2130G>A		intron_variant			NP_001230929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIB	ENST00000595883.6	c.490+2130G>A		intron_variant		1	NM_003121.5	ENSP00000471921	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79163 AN: 151880 Hom.: 23598 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.521 AC: 79172 AN: 152000 Hom.: 23599 Cov.: 32 AF XY: 0.523 AC XY: 38901 AN XY: 74318

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.510

Alfa AF: 0.581 Hom.: 3024

Bravo AF: 0.497

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.60

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: rs56235776; hg19: chr19-50929142;