rs8108811

chr19-50424101-G-Achr19-50424101-G-C

Variant summary

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

The NM_003121.5(SPIB):c.490+346G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,914 control chromosomes in the GnomAD database, including 31,941 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 0.62 (31941 hom., cov: 30)
• Consequence: SPIB NM_003121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPIB	NM_003121.5	c.490+346G>A		intron_variant		ENST00000595883.6
SPIB	NM_001243998.2	c.217+346G>A		intron_variant
SPIB	NM_001243999.2	c.486+350G>A		intron_variant
SPIB	NM_001244000.2	c.397+346G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIB	ENST00000595883.6	c.490+346G>A		intron_variant		1	NM_003121.5	P1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93843 AN: 151796 Hom.: 31940 Cov.: 30

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.618 AC: 93882 AN: 151914 Hom.: 31941 Cov.: 30 AF XY: 0.619 AC XY: 45969 AN XY: 74270

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.604

Alfa AF: 0.703 Hom.: 7775

Bravo AF: 0.591

Asia WGS AF: 0.442 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.45
Dann	Benign	0.37

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: rs8108811; hg19: chr19-50927358;