rs1506418

Variant names:

• chr18-63720078-G-A
• rs1506418
• NM_001370475.1:c.541G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370475.1(SERPINB11):​c.541G>A​(p.Ala181Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,600,626 control chromosomes in the GnomAD database, including 83,935 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 0.37 (11310 hom., cov: 33)
  • Exomes 𝑓: 0.31 (72625 hom.)
• Consequence: SERPINB11 NM_001370475.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.60

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.375875E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.541G>A	p.Ala181Thr	missense_variant	Exon 6 of 8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.541G>A	p.Ala181Thr	missense_variant	Exon 7 of 9		NP_536723.2
SERPINB11	NM_001291279.2	c.16G>A	p.Ala6Thr	missense_variant	Exon 5 of 7		NP_001278208.1
SERPINB11	NM_001291278.2	c.358-753G>A		intron_variant	Intron 4 of 5		NP_001278207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6	c.541G>A	p.Ala181Thr	missense_variant	Exon 6 of 8	2	NM_001370475.1	ENSP00000441497.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56339 AN: 151794 Hom.: 11282 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.355

GnomAD2 exomes AF: 0.364 AC: 89590 AN: 246142 AF XY: 0.354

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.606

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.305 AC: 441919 AN: 1448714 Hom.: 72625 Cov.: 31 AF XY: 0.306 AC XY: 220970 AN XY: 721040

Gnomad4 AFR exome AF: 0.509 AC: 16761 AN: 32902

Gnomad4 AMR exome AF: 0.486 AC: 21366 AN: 43962

Gnomad4 ASJ exome AF: 0.339 AC: 8767 AN: 25896

Gnomad4 EAS exome AF: 0.586 AC: 23074 AN: 39402

Gnomad4 SAS exome AF: 0.380 AC: 32389 AN: 85346

Gnomad4 FIN exome AF: 0.332 AC: 17704 AN: 53264

Gnomad4 NFE exome AF: 0.273 AC: 300587 AN: 1102362

Gnomad4 Remaining exome AF: 0.323 AC: 19323 AN: 59848

GnomAD4 genome AF: 0.371 AC: 56409 AN: 151912 Hom.: 11310 Cov.: 33 AF XY: 0.376 AC XY: 27950 AN XY: 74256

Gnomad4 AFR AF: 0.499 AC: 0.499131 AN: 0.499131

Gnomad4 AMR AF: 0.407 AC: 0.407228 AN: 0.407228

Gnomad4 ASJ AF: 0.345 AC: 0.345444 AN: 0.345444

Gnomad4 EAS AF: 0.608 AC: 0.608098 AN: 0.608098

Gnomad4 SAS AF: 0.380 AC: 0.380448 AN: 0.380448

Gnomad4 FIN AF: 0.331 AC: 0.330553 AN: 0.330553

Gnomad4 NFE AF: 0.276 AC: 0.275505 AN: 0.275505

Gnomad4 OTH AF: 0.359 AC: 0.359242 AN: 0.359242

Alfa AF: 0.315 Hom.: 37200

Bravo AF: 0.386

TwinsUK AF: 0.273 AC: 1012

ALSPAC AF: 0.269 AC: 1037

ESP6500AA AF: 0.495 AC: 1799

ESP6500EA AF: 0.272 AC: 2217

ExAC AF: 0.361 AC: 43581

Asia WGS AF: 0.508 AC: 1763 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T;.;T
MetaRNN	Benign	0.00044	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	.;.;D
REVEL	Uncertain	0.48
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	.;D;D
Vest4		0.25, 0.25
MPC		0.081
ClinPred		0.022	T
GERP RS		5.5
Mutation Taster		=75/25	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

Publications

LitVar

Other links and lift over

dbSNP: rs1506418; hg19: chr18-61387312; COSMIC: COSV107493258;