18-63723336-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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 -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.

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.1116T>G	p.Leu372Leu	synonymous	Exon 8 of 8	NP_001357404.1	F5GYW9
	SERPINB11	NM_080475.5		c.1116T>G	p.Leu372Leu	synonymous	Exon 9 of 9	NP_536723.2	Q96P15-1
	SERPINB11	NM_001291278.2		c.855T>G	p.Leu285Leu	synonymous	Exon 6 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.1116T>G	p.Leu372Leu	synonymous	Exon 8 of 8	ENSP00000441497.1	F5GYW9
	SERPINB11	ENST00000382749.9	TSL:1	c.1116T>G	p.Leu372Leu	synonymous	Exon 9 of 9	ENSP00000421854.1	Q96P15-1
	SERPINB11	ENST00000623262.3	TSL:1	c.855T>G	p.Leu285Leu	synonymous	Exon 5 of 5	ENSP00000485532.1	Q96P15-2

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

GnomAD2 exomes AF: 0.723 AC: 179780 AN: 248564 AF XY: 0.722

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 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

African (AFR) AF: 0.569 AC: 19042 AN: 33464

American (AMR) AF: 0.742 AC: 33189 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18594 AN: 26124

East Asian (EAS) AF: 0.854 AC: 33886 AN: 39696

South Asian (SAS) AF: 0.690 AC: 59534 AN: 86234

European-Finnish (FIN) AF: 0.751 AC: 40108 AN: 53398

Middle Eastern (MID) AF: 0.681 AC: 3928 AN: 5764

European-Non Finnish (NFE) AF: 0.730 AC: 811593 AN: 1111618

Other (OTH) AF: 0.716 AC: 43223 AN: 60370

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

African (AFR) AF: 0.575 AC: 23806 AN: 41414

American (AMR) AF: 0.713 AC: 10897 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2483 AN: 3470

East Asian (EAS) AF: 0.845 AC: 4371 AN: 5172

South Asian (SAS) AF: 0.691 AC: 3327 AN: 4814

European-Finnish (FIN) AF: 0.754 AC: 7951 AN: 10552

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49324 AN: 67968

Other (OTH) AF: 0.681 AC: 1435 AN: 2106

Alfa AF: 0.715 Hom.: 124813

Bravo AF: 0.683

Asia WGS AF: 0.763 AC: 2650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.0
DANN	Benign	0.69
PhyloP100		0.041
Mutation Taster		=98/2	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: rs953695; hg19: chr18-61390570; COSMIC: COSV66956865; COSMIC: COSV66956865;