rs11546996

Variant names:

• chr19-50423008-G-A
• rs11546996
• NM_003121.5:c.310G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-50423008-G-A
• chr19-50423008-G-C
• chr19-50423008-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003121.5(SPIB):​c.310G>A​(p.Ala104Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,523,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SPIB NM_003121.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 25 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013177156).
• BS2: High AC in GnomAd4 at 113 AD gene.

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.310G>A	p.Ala104Thr	missense	Exon 4 of 6	NP_003112.2
	SPIB	NM_001243999.2		c.310G>A	p.Ala104Thr	missense	Exon 4 of 6	NP_001230928.1
	SPIB	NM_001244000.2		c.252G>A	p.Leu84Leu	synonymous	Exon 4 of 6	NP_001230929.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIB	ENST00000595883.6	TSL:1 MANE Select	c.310G>A	p.Ala104Thr	missense	Exon 4 of 6	ENSP00000471921.1
	ENSG00000142539	ENST00000599632.1	TSL:5	c.712G>A	p.Ala238Thr	missense	Exon 8 of 10	ENSP00000473233.1
	SPIB	ENST00000270632.7	TSL:1	c.310G>A	p.Ala104Thr	missense	Exon 4 of 6	ENSP00000270632.7

Frequencies

GnomAD3 genomes AF: 0.000747 AC: 113 AN: 151314 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000360 AC: 70 AN: 194396 AF XY: 0.000282

Gnomad AFR exome AF: 0.00256

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000119 AC: 163 AN: 1372538 Hom.: 0 Cov.: 27 AF XY: 0.000114 AC XY: 77 AN XY: 678316

African (AFR) AF: 0.00357 AC: 109 AN: 30572

American (AMR) AF: 0.00122 AC: 40 AN: 32780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21634

East Asian (EAS) AF: 0.00 AC: 0 AN: 38568

South Asian (SAS) AF: 0.00 AC: 0 AN: 75932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4690

European-Non Finnish (NFE) AF: 0.00000659 AC: 7 AN: 1061966

Other (OTH) AF: 0.000124 AC: 7 AN: 56438

GnomAD4 genome AF: 0.000746 AC: 113 AN: 151432 Hom.: 0 Cov.: 27 AF XY: 0.000771 AC XY: 57 AN XY: 73958

African (AFR) AF: 0.00259 AC: 107 AN: 41322

American (AMR) AF: 0.000394 AC: 6 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67732

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000112 Hom.: 4146

ExAC AF: 0.000341 AC: 41

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.2
DANN	Benign	0.58
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.80
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.035
Sift	Benign	0.51	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.056
MVP		0.31
MPC		0.023
ClinPred		0.0030	T
GERP RS		-2.1
Varity_R		0.036
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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: rs11546996; hg19: chr19-50926265;