19-50428707-G-A

Variant names:

• chr19-50428707-G-A
• rs1137895
• NM_003121.5:c.*371G>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.*371G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPIB NM_003121.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• 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]

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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPIB	NM_003121.5	c.*371G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000595883.6	NP_003112.2
SPIB	NM_001244000.2	c.*371G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001230929.2
SPIB	NM_001243999.2	c.*622G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001230928.1
SPIB	NM_001243998.2	c.*371G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001230927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPIB	ENST00000595883.6	c.*371G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_003121.5	ENSP00000471921.1
SPIB	ENST00000270632.7	c.*622G>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000270632.7
SPIB	ENST00000439922.6	c.*371G>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000391877.2
SPIB	ENST00000596074.5	c.*711G>A		downstream_gene_variant		2		ENSP00000470970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 89006 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44758

African (AFR) AF: 0.00 AC: 0 AN: 3258

American (AMR) AF: 0.00 AC: 0 AN: 2556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3580

East Asian (EAS) AF: 0.00 AC: 0 AN: 7430

South Asian (SAS) AF: 0.00 AC: 0 AN: 1896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58350

Other (OTH) AF: 0.00 AC: 0 AN: 6258

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.93
PhyloP100		-0.13

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: rs1137895; hg19: chr19-50931964;