18-63892477-C-T

Variant names:

• chr18-63892477-C-T
• rs9630856
• NM_002575.3:c.168+865C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002575.3(SERPINB2):​c.168+865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,110 control chromosomes in the GnomAD database, including 5,774 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 0.26 (5774 hom., cov: 32)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: SERPINB2 NM_002575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 8 publications found

Genes affected

SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904356 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.168+865C>T		intron_variant	Intron 2 of 7	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.168+865C>T		intron_variant	Intron 3 of 8		NP_001137290.1
SERPINB2	XM_024451192.2	c.168+865C>T		intron_variant	Intron 2 of 7		XP_024306960.1
LOC124904356	XR_007066466.1	n.183+144G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.168+865C>T		intron_variant	Intron 2 of 7	1	NM_002575.3	ENSP00000299502.4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40158 AN: 151984 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.264 AC: 40214 AN: 152102 Hom.: 5774 Cov.: 32 AF XY: 0.268 AC XY: 19941 AN XY: 74374

African (AFR) AF: 0.287 AC: 11886 AN: 41470

American (AMR) AF: 0.362 AC: 5530 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3466

East Asian (EAS) AF: 0.479 AC: 2480 AN: 5176

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4826

European-Finnish (FIN) AF: 0.234 AC: 2469 AN: 10568

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14942 AN: 67988

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.236 Hom.: 16681

Bravo AF: 0.277

Asia WGS AF: 0.388 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.51
PhyloP100		-0.89
Mutation Taster		=100/0	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: rs9630856; hg19: chr18-61559711;