19-50423485-A-T

Variant names:

• chr19-50423485-A-T
• rs3745516
• NM_003121.5:c.340-120A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003121.5(SPIB):​c.340-120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000008 in 1,249,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: SPIB NM_003121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003121.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	NM_003121.5	MANE Select	c.340-120A>T		intron	N/A	NP_003112.2	Q01892-1
	SPIB	NM_001244000.2		c.282-155A>T		intron	N/A	NP_001230929.2
	SPIB	NM_001243999.2		c.340-120A>T		intron	N/A	NP_001230928.1	Q01892-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	ENST00000595883.6	TSL:1 MANE Select	c.340-120A>T		intron	N/A	ENSP00000471921.1	Q01892-1
	ENSG00000142539	ENST00000599632.1	TSL:5	c.742-120A>T		intron	N/A	ENSP00000473233.1	M0R3H8
	SPIB	ENST00000270632.7	TSL:1	c.340-120A>T		intron	N/A	ENSP00000270632.7	Q01892-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1249922 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 617330

African (AFR) AF: 0.00 AC: 0 AN: 28378

American (AMR) AF: 0.00 AC: 0 AN: 30070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19558

East Asian (EAS) AF: 0.00 AC: 0 AN: 37420

South Asian (SAS) AF: 0.00 AC: 0 AN: 67876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 965024

Other (OTH) AF: 0.00 AC: 0 AN: 52558

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.44
PhyloP100		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3745516; hg19: chr19-50926742;