18-63712604-G-T

Variant names:

• chr18-63712604-G-T
• rs4940595
• NM_001370475.1:c.268G>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001370475.1(SERPINB11):​c.268G>T​(p.Glu90*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,613,366 control chromosomes in the GnomAD database, including 386,126 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.63 (30894 hom., cov: 32)
  • Exomes 𝑓: 0.69 (355232 hom.)
• Consequence: SERPINB11 NM_001370475.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

SERPINB11 (HGNC:14221): (serpin family B member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.268G>T	p.Glu90*	stop_gained	Exon 4 of 8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.268G>T	p.Glu90*	stop_gained	Exon 5 of 9		NP_536723.2
SERPINB11	NM_001291278.2	c.268G>T	p.Glu90*	stop_gained	Exon 4 of 6		NP_001278207.1
SERPINB11	NM_001291279.2	c.-140G>T		5_prime_UTR_variant	Exon 4 of 7		NP_001278208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6	c.268G>T	p.Glu90*	stop_gained	Exon 4 of 8	2	NM_001370475.1	ENSP00000441497.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95513 AN: 151926 Hom.: 30877 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.693 AC: 1012369 AN: 1461322 Hom.: 355232 Cov.: 42 AF XY: 0.692 AC XY: 502707 AN XY: 726940

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.629 AC: 95561 AN: 152044 Hom.: 30894 Cov.: 32 AF XY: 0.623 AC XY: 46346 AN XY: 74342

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.641

Alfa AF: 0.692 Hom.: 61896

Bravo AF: 0.614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Pathogenic	29
Vest4		0.35, 0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4940595; hg19: chr18-61379838;