6-2836133-G-T

Variant names:

• chr6-2836133-G-T
• rs890454027
• NM_030666.4:c.542C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030666.4(SERPINB1):​c.542C>A​(p.Thr181Lys) variant causes a missense 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. 17/22 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. T181M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB1 NM_030666.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06644946).

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.542C>A	p.Thr181Lys	missense	Exon 5 of 7	NP_109591.1	P30740-1
	SERPINB1	NR_073111.2		n.734C>A		non_coding_transcript_exon	Exon 6 of 8
	SERPINB1	NR_073112.2		n.602C>A		non_coding_transcript_exon	Exon 5 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB1	ENST00000380739.6	TSL:1 MANE Select	c.542C>A	p.Thr181Lys	missense	Exon 5 of 7	ENSP00000370115.5	P30740-1
	SERPINB1	ENST00000878907.1		c.542C>A	p.Thr181Lys	missense	Exon 4 of 6	ENSP00000548966.1
	SERPINB1	ENST00000878908.1		c.542C>A	p.Thr181Lys	missense	Exon 5 of 7	ENSP00000548967.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.30
DANN	Benign	0.30
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.040	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.32	N
PhyloP100		-0.0030
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.17
Sift	Benign	0.64	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.093
MutPred		0.42		Gain of MoRF binding (P = 0.0297)
MVP		0.43
MPC		0.21
ClinPred		0.023	T
GERP RS		0.0076
Varity_R		0.060
gMVP		0.54
Mutation Taster		=76/24	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: rs890454027; hg19: chr6-2836367;