rs8108811

Variant names:

• chr19-50424101-G-A
• rs8108811
• NM_003121.5:c.490+346G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50424101-G-A
• chr19-50424101-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ENSG00000142539 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPIB	NM_003121.5	c.490+346G>A		intron_variant	Intron 5 of 5	ENST00000595883.6	NP_003112.2
SPIB	NM_001244000.2	c.397+346G>A		intron_variant	Intron 5 of 5		NP_001230929.2
SPIB	NM_001243999.2	c.486+350G>A		intron_variant	Intron 5 of 5		NP_001230928.1
SPIB	NM_001243998.2	c.217+346G>A		intron_variant	Intron 4 of 4		NP_001230927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIB	ENST00000595883.6	c.490+346G>A		intron_variant	Intron 5 of 5	1	NM_003121.5	ENSP00000471921.1
ENSG00000142539	ENST00000599632.1	c.892+346G>A		intron_variant	Intron 9 of 9	5		ENSP00000473233.1

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

African (AFR) AF: 0.357 AC: 14798 AN: 41398

American (AMR) AF: 0.661 AC: 10061 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5162

South Asian (SAS) AF: 0.605 AC: 2914 AN: 4816

European-Finnish (FIN) AF: 0.832 AC: 8809 AN: 10594

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51819 AN: 67928

Other (OTH) AF: 0.604 AC: 1273 AN: 2108

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
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8108811; hg19: chr19-50927358;