18-63723336-T-G

Variant names:

• chr18-63723336-T-G
• rs953695
• NM_001370475.1:c.1116T>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370475.1(SERPINB11):​c.1116T>G​(p.Leu372Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,613,374 control chromosomes in the GnomAD database, including 424,267 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 0.69 (36434 hom., cov: 31)
  • Exomes 𝑓: 0.73 (387833 hom.)
• Consequence: SERPINB11 NM_001370475.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.041 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB11	NM_001370475.1	c.1116T>G	p.Leu372Leu	synonymous_variant	Exon 8 of 8	ENST00000544088.6	NP_001357404.1
SERPINB11	NM_080475.5	c.1116T>G	p.Leu372Leu	synonymous_variant	Exon 9 of 9		NP_536723.2
SERPINB11	NM_001291278.2	c.855T>G	p.Leu285Leu	synonymous_variant	Exon 6 of 6		NP_001278207.1
SERPINB11	NM_001291279.2	c.591T>G	p.Leu197Leu	synonymous_variant	Exon 7 of 7		NP_001278208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB11	ENST00000544088.6	c.1116T>G	p.Leu372Leu	synonymous_variant	Exon 8 of 8	2	NM_001370475.1	ENSP00000441497.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104546 AN: 151870 Hom.: 36417 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.685

GnomAD3 exomes AF: 0.723 AC: 179780 AN: 248564 Hom.: 65408 AF XY: 0.722 AC XY: 97291 AN XY: 134810

Gnomad AFR exome AF: 0.578

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.712

Gnomad EAS exome AF: 0.846

Gnomad SAS exome AF: 0.685

Gnomad FIN exome AF: 0.753

Gnomad NFE exome AF: 0.722

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.727 AC: 1063097 AN: 1461386 Hom.: 387833 Cov.: 56 AF XY: 0.726 AC XY: 527953 AN XY: 726984

Gnomad4 AFR exome AF: 0.569

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.690

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.688 AC: 104608 AN: 151988 Hom.: 36434 Cov.: 31 AF XY: 0.691 AC XY: 51374 AN XY: 74308

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.681

Alfa AF: 0.718 Hom.: 52249

Bravo AF: 0.683

Asia WGS AF: 0.763 AC: 2650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.0
DANN	Benign	0.69

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: rs953695; hg19: chr18-61390570; COSMIC: COSV66956865; COSMIC: COSV66956865;