NM_003121.5:c.339+271C>T

Variant names:

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

Variant summary

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

The NM_003121.5(SPIB):​c.339+271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 505,606 control chromosomes in the GnomAD database, including 3,144 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 0.11 (922 hom., cov: 31)
  • Exomes 𝑓: 0.11 (2222 hom.)
• Consequence: SPIB NM_003121.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 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.339+271C>T		intron	N/A	NP_003112.2
	SPIB	NM_001244000.2		c.281+271C>T		intron	N/A	NP_001230929.2
	SPIB	NM_001243999.2		c.339+271C>T		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>T		intron	N/A	ENSP00000471921.1
	ENSG00000142539	ENST00000599632.1	TSL:5	c.741+271C>T		intron	N/A	ENSP00000473233.1
	SPIB	ENST00000270632.7	TSL:1	c.339+271C>T		intron	N/A	ENSP00000270632.7

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16617 AN: 151992 Hom.: 920 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.110 AC: 38976 AN: 353494 Hom.: 2222 AF XY: 0.111 AC XY: 20314 AN XY: 182366

African (AFR) AF: 0.105 AC: 1094 AN: 10380

American (AMR) AF: 0.137 AC: 1785 AN: 12986

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 1734 AN: 11670

East Asian (EAS) AF: 0.127 AC: 3397 AN: 26782

South Asian (SAS) AF: 0.113 AC: 2638 AN: 23320

European-Finnish (FIN) AF: 0.0739 AC: 1893 AN: 25612

Middle Eastern (MID) AF: 0.182 AC: 307 AN: 1684

European-Non Finnish (NFE) AF: 0.108 AC: 23726 AN: 219300

Other (OTH) AF: 0.110 AC: 2402 AN: 21760

GnomAD4 genome AF: 0.109 AC: 16621 AN: 152112 Hom.: 922 Cov.: 31 AF XY: 0.108 AC XY: 8005 AN XY: 74342

African (AFR) AF: 0.110 AC: 4574 AN: 41512

American (AMR) AF: 0.125 AC: 1916 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5176

South Asian (SAS) AF: 0.117 AC: 562 AN: 4822

European-Finnish (FIN) AF: 0.0642 AC: 678 AN: 10566

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7292 AN: 67970

Other (OTH) AF: 0.119 AC: 251 AN: 2110

Alfa AF: 0.115 Hom.: 668

Bravo AF: 0.114

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		0.32
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: rs34944112; hg19: chr19-50926565;