chr19-50428707-G-C

Variant names:

• chr19-50428707-G-C
• rs1137895
• NM_003121.5:c.*371G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	NM_003121.5	MANE Select	c.*371G>C		3_prime_UTR	Exon 6 of 6	NP_003112.2
	SPIB	NM_001244000.2		c.*371G>C		3_prime_UTR	Exon 6 of 6	NP_001230929.2
	SPIB	NM_001243999.2		c.*622G>C		3_prime_UTR	Exon 6 of 6	NP_001230928.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	ENST00000595883.6	TSL:1 MANE Select	c.*371G>C		3_prime_UTR	Exon 6 of 6	ENSP00000471921.1
	SPIB	ENST00000270632.7	TSL:1	c.*622G>C		3_prime_UTR	Exon 6 of 6	ENSP00000270632.7
	SPIB	ENST00000439922.6	TSL:2	c.*371G>C		3_prime_UTR	Exon 5 of 5	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

African (AFR) AF: 0.564 AC: 1831 AN: 3248

American (AMR) AF: 0.290 AC: 738 AN: 2546

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1222 AN: 3554

East Asian (EAS) AF: 0.126 AC: 934 AN: 7424

South Asian (SAS) AF: 0.212 AC: 402 AN: 1892

European-Finnish (FIN) AF: 0.148 AC: 772 AN: 5204

Middle Eastern (MID) AF: 0.350 AC: 161 AN: 460

European-Non Finnish (NFE) AF: 0.207 AC: 12035 AN: 58176

Other (OTH) AF: 0.256 AC: 1598 AN: 6244

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

African (AFR) AF: 0.558 AC: 23137 AN: 41450

American (AMR) AF: 0.304 AC: 4653 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3468

East Asian (EAS) AF: 0.166 AC: 857 AN: 5174

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4822

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10596

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14464 AN: 67970

Other (OTH) AF: 0.317 AC: 669 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.65
PhyloP100		-0.13
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: rs1137895; hg19: chr19-50931964;