chr19-50423308-C-A

Variant names:

• chr19-50423308-C-A
• rs34944112
• NM_003121.5:c.339+271C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003121.5(SPIB):​c.339+271C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 353,784 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: 0.0000028 (0 hom.)
• Consequence: SPIB NM_003121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	NM_003121.5	MANE Select	c.339+271C>A		intron	N/A	NP_003112.2
	SPIB	NM_001244000.2		c.281+271C>A		intron	N/A	NP_001230929.2
	SPIB	NM_001243999.2		c.339+271C>A		intron	N/A	NP_001230928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	ENST00000595883.6	TSL:1 MANE Select	c.339+271C>A		intron	N/A	ENSP00000471921.1
	ENSG00000142539	ENST00000599632.1	TSL:5	c.741+271C>A		intron	N/A	ENSP00000473233.1
	SPIB	ENST00000270632.7	TSL:1	c.339+271C>A		intron	N/A	ENSP00000270632.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000283 AC: 1 AN: 353784 Hom.: 0 AF XY: 0.00000548 AC XY: 1 AN XY: 182512

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10388

American (AMR) AF: 0.00 AC: 0 AN: 12998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11688

East Asian (EAS) AF: 0.00 AC: 0 AN: 26810

South Asian (SAS) AF: 0.00 AC: 0 AN: 23356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1684

European-Non Finnish (NFE) AF: 0.00000456 AC: 1 AN: 219466

Other (OTH) AF: 0.00 AC: 0 AN: 21770

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		0.32

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: rs34944112; hg19: chr19-50926565;