19-50428707-G-C

Position:

• chr19-50428707-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003121.5(SPIB):​c.*371G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 240,828 control chromosomes in the GnomAD database, including 12,267 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 0.32 (9627 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2640 hom.)
• Consequence: SPIB NM_003121.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIB	NM_003121.5	c.*371G>C		3_prime_UTR_variant	6/6	ENST00000595883.6	NP_003112.2
SPIB	NM_001244000.2	c.*371G>C		3_prime_UTR_variant	6/6		NP_001230929.2
SPIB	NM_001243999.2	c.*622G>C		3_prime_UTR_variant	6/6		NP_001230928.1
SPIB	NM_001243998.2	c.*371G>C		3_prime_UTR_variant	5/5		NP_001230927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIB	ENST00000595883.6	c.*371G>C		3_prime_UTR_variant	6/6	1	NM_003121.5	ENSP00000471921.1
SPIB	ENST00000270632.7	c.*622G>C		3_prime_UTR_variant	6/6	1		ENSP00000270632.7
SPIB	ENST00000439922.6	c.*371G>C		3_prime_UTR_variant	5/5	2		ENSP00000391877.2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48190 AN: 151962 Hom.: 9602 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.222 AC: 19693 AN: 88748 Hom.: 2640 Cov.: 0 AF XY: 0.223 AC XY: 9948 AN XY: 44642

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.317 AC: 48258 AN: 152080 Hom.: 9627 Cov.: 32 AF XY: 0.311 AC XY: 23159 AN XY: 74358

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.317

Alfa AF: 0.280 Hom.: 925

Bravo AF: 0.336

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1137895; hg19: chr19-50931964;