NM_030666.4:c.568-9A>G

Variant names:

• chr6-2836032-T-C
• rs385955
• NM_030666.4:c.568-9A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030666.4(SERPINB1):​c.568-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SERPINB1 NM_030666.4 intron
• Scores: Splicing: ADA: 0.9969
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 9 publications found

Genes affected

SERPINB1 (HGNC:3311): (serpin family B member 1) The protein encoded by this gene is a member of the serpin family of proteinase inhibitors. Members of this family maintain homeostasis by neutralizing overexpressed proteinase activity through their function as suicide substrates. This protein inhibits the neutrophil-derived proteinases neutrophil elastase, cathepsin G, and proteinase-3 and thus protects tissues from damage at inflammatory sites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030666.4. 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
	SERPINB1	NM_030666.4	MANE Select	c.568-9A>G		intron	N/A	NP_109591.1	P30740-1
	SERPINB1	NR_073111.2		n.760-9A>G		intron	N/A
	SERPINB1	NR_073112.2		n.628-13A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB1	ENST00000380739.6	TSL:1 MANE Select	c.568-9A>G		intron	N/A	ENSP00000370115.5	P30740-1
	SERPINB1	ENST00000878907.1		c.568-9A>G		intron	N/A	ENSP00000548966.1
	SERPINB1	ENST00000878908.1		c.568-9A>G		intron	N/A	ENSP00000548967.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Pathogenic	34
DANN	Benign	0.72
PhyloP100		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.98		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs385955; hg19: chr6-2836266;