19-50422138-G-A

Variant names:

• chr19-50422138-G-A
• rs62116060
• NM_003121.5:c.52-335G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003121.5(SPIB):​c.52-335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,114 control chromosomes in the GnomAD database, including 31,673 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 0.61 (31673 hom., cov: 33)
• Consequence: SPIB NM_003121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

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.52-335G>A		intron	N/A	NP_003112.2
	SPIB	NM_001244000.2		c.-7-335G>A		intron	N/A	NP_001230929.2
	SPIB	NM_001243999.2		c.52-335G>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.52-335G>A		intron	N/A	ENSP00000471921.1
	ENSG00000142539	ENST00000599632.1	TSL:5	c.454-335G>A		intron	N/A	ENSP00000473233.1
	SPIB	ENST00000270632.7	TSL:1	c.52-335G>A		intron	N/A	ENSP00000270632.7

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93135 AN: 151994 Hom.: 31673 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.613 AC: 93174 AN: 152114 Hom.: 31673 Cov.: 33 AF XY: 0.614 AC XY: 45676 AN XY: 74364

African (AFR) AF: 0.338 AC: 14001 AN: 41464

American (AMR) AF: 0.658 AC: 10067 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1098 AN: 5156

South Asian (SAS) AF: 0.601 AC: 2900 AN: 4828

European-Finnish (FIN) AF: 0.832 AC: 8822 AN: 10602

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51863 AN: 67988

Other (OTH) AF: 0.604 AC: 1275 AN: 2112

Alfa AF: 0.674 Hom.: 4349

Bravo AF: 0.585

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.64
PhyloP100		0.14
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: rs62116060; hg19: chr19-50925395;