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
• Publications: 23 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370475.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB11	NM_001370475.1	MANE Select	c.541G>A	p.Ala181Thr	missense	Exon 6 of 8	NP_001357404.1
	SERPINB11	NM_080475.5		c.541G>A	p.Ala181Thr	missense	Exon 7 of 9	NP_536723.2
	SERPINB11	NM_001291279.2		c.16G>A	p.Ala6Thr	missense	Exon 5 of 7	NP_001278208.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB11	ENST00000544088.6	TSL:2 MANE Select	c.541G>A	p.Ala181Thr	missense	Exon 6 of 8	ENSP00000441497.1
	SERPINB11	ENST00000382749.9	TSL:1	c.541G>A	p.Ala181Thr	missense	Exon 7 of 9	ENSP00000421854.1
	SERPINB11	ENST00000467649.2	TSL:1	n.689G>A		non_coding_transcript_exon	Exon 7 of 10

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

African (AFR) AF: 0.509 AC: 16761 AN: 32902

American (AMR) AF: 0.486 AC: 21366 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8767 AN: 25896

East Asian (EAS) AF: 0.586 AC: 23074 AN: 39402

South Asian (SAS) AF: 0.380 AC: 32389 AN: 85346

European-Finnish (FIN) AF: 0.332 AC: 17704 AN: 53264

Middle Eastern (MID) AF: 0.340 AC: 1948 AN: 5732

European-Non Finnish (NFE) AF: 0.273 AC: 300587 AN: 1102362

Other (OTH) 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

African (AFR) AF: 0.499 AC: 20675 AN: 41422

American (AMR) AF: 0.407 AC: 6220 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1198 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3139 AN: 5162

South Asian (SAS) AF: 0.380 AC: 1833 AN: 4818

European-Finnish (FIN) AF: 0.331 AC: 3488 AN: 10552

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18709 AN: 67908

Other (OTH) AF: 0.359 AC: 758 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
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
MetaRNN	Benign	0.00044	T
MetaSVM	Benign	-0.95	T
PhyloP100		7.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.48
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		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

Other links and lift over

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