18-63712604-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB11	NM_001370475.1	MANE Select	c.268G>T	p.Glu90*	stop_gained	Exon 4 of 8	NP_001357404.1	F5GYW9
	SERPINB11	NM_080475.5		c.268G>T	p.Glu90*	stop_gained	Exon 5 of 9	NP_536723.2	Q96P15-1
	SERPINB11	NM_001291278.2		c.268G>T	p.Glu90*	stop_gained	Exon 4 of 6	NP_001278207.1	A0A096LPD5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB11	ENST00000544088.6	TSL:2 MANE Select	c.268G>T	p.Glu90*	stop_gained	Exon 4 of 8	ENSP00000441497.1	F5GYW9
	SERPINB11	ENST00000382749.9	TSL:1	c.268G>T	p.Glu90*	stop_gained	Exon 5 of 9	ENSP00000421854.1	Q96P15-1
	SERPINB11	ENST00000623262.3	TSL:1	c.268G>T	p.Glu90*	stop_gained	Exon 3 of 5	ENSP00000485532.1	Q96P15-2

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

African (AFR) AF: 0.489 AC: 16354 AN: 33452

American (AMR) AF: 0.513 AC: 22930 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 17239 AN: 26130

East Asian (EAS) AF: 0.414 AC: 16409 AN: 39682

South Asian (SAS) AF: 0.619 AC: 53352 AN: 86236

European-Finnish (FIN) AF: 0.667 AC: 35630 AN: 53398

Middle Eastern (MID) AF: 0.659 AC: 3802 AN: 5768

European-Non Finnish (NFE) AF: 0.725 AC: 805900 AN: 1111580

Other (OTH) AF: 0.675 AC: 40753 AN: 60354

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

African (AFR) AF: 0.501 AC: 20761 AN: 41460

American (AMR) AF: 0.593 AC: 9061 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2272 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2002 AN: 5152

South Asian (SAS) AF: 0.619 AC: 2975 AN: 4808

European-Finnish (FIN) AF: 0.670 AC: 7082 AN: 10578

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49241 AN: 67972

Other (OTH) AF: 0.641 AC: 1353 AN: 2112

Alfa AF: 0.684 Hom.: 79195

Bravo AF: 0.614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Pathogenic	29
PhyloP100		-2.1
Vest4		0.35

Splicing

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

Other links and lift over

dbSNP: rs4940595; hg19: chr18-61379838;