rs1395268

Positions:

• chr18-63710345-A-C
• chr18-63710345-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370475.1(SERPINB11):​c.152A>C​(p.Glu51Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,611,812 control chromosomes in the GnomAD database, including 559,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51393 hom., cov: 32)
  • Exomes 𝑓: 0.83 (507820 hom.)
• Consequence: SERPINB11 NM_001370475.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.694

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1503892E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB11	NM_001370475.1	c.152A>C	p.Glu51Ala	missense_variant	2/8	ENST00000544088.6
SERPINB11	NM_080475.5	c.152A>C	p.Glu51Ala	missense_variant	3/9
SERPINB11	NM_001291278.2	c.152A>C	p.Glu51Ala	missense_variant	2/6
SERPINB11	NM_001291279.2	c.-256A>C		5_prime_UTR_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB11	ENST00000544088.6	c.152A>C	p.Glu51Ala	missense_variant	2/8	2	NM_001370475.1	P1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124890 AN: 152016 Hom.: 51354 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.825

GnomAD3 exomes AF: 0.836 AC: 206837 AN: 247268 Hom.: 86732 AF XY: 0.833 AC XY: 111818 AN XY: 134184

Gnomad AFR exome AF: 0.788

Gnomad AMR exome AF: 0.888

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.901

Gnomad SAS exome AF: 0.818

Gnomad FIN exome AF: 0.830

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.828

GnomAD4 exome AF: 0.834 AC: 1216830 AN: 1459678 Hom.: 507820 Cov.: 42 AF XY: 0.833 AC XY: 604661 AN XY: 726134

Gnomad4 AFR exome AF: 0.787

Gnomad4 AMR exome AF: 0.881

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.901

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.828

GnomAD4 genome AF: 0.822 AC: 124987 AN: 152134 Hom.: 51393 Cov.: 32 AF XY: 0.821 AC XY: 61094 AN XY: 74370

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.827

Alfa AF: 0.827 Hom.: 128281

Bravo AF: 0.821

TwinsUK AF: 0.840 AC: 3114

ALSPAC AF: 0.837 AC: 3227

ESP6500AA AF: 0.795 AC: 2977

ESP6500EA AF: 0.829 AC: 6813

ExAC AF: 0.836 AC: 100970

Asia WGS AF: 0.870 AC: 3024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	8.4
DANN	Benign	0.11
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.032	T;.;T;T;T
MetaRNN	Benign	0.0000012	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.37	T
Sift4G	Benign	1.0	T;T;T;T;T
Vest4		0.044, 0.10, 0.16
MPC		0.012
ClinPred		0.012	T
GERP RS		4.3
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1395268; hg19: chr18-61377579; COSMIC: COSV66957181; COSMIC: COSV66957181;