18-63891422-C-G

Variant names:

• chr18-63891422-C-G
• rs6095
• NM_002575.3:c.-9-14C>G

Variant summary

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

The NM_002575.3(SERPINB2):​c.-9-14C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,611,838 control chromosomes in the GnomAD database, including 63,354 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 0.37 (12951 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50403 hom.)
• Consequence: SERPINB2 NM_002575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002575.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	NM_002575.3	MANE Select	c.-9-14C>G		intron	N/A	NP_002566.1
	SERPINB2	NM_001143818.2		c.-9-14C>G		intron	N/A	NP_001137290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	ENST00000299502.9	TSL:1 MANE Select	c.-9-14C>G		intron	N/A	ENSP00000299502.4
	SERPINB2	ENST00000457692.5	TSL:5	c.-9-14C>G		intron	N/A	ENSP00000401645.1
	SERPINB2	ENST00000413956.5	TSL:5	c.-9-14C>G		intron	N/A	ENSP00000402386.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55761 AN: 151842 Hom.: 12910 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.307 AC: 76955 AN: 250466 AF XY: 0.293

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.472

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.248 AC: 362636 AN: 1459878 Hom.: 50403 Cov.: 32 AF XY: 0.248 AC XY: 179820 AN XY: 726274

African (AFR) AF: 0.661 AC: 22077 AN: 33382

American (AMR) AF: 0.434 AC: 19305 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4918 AN: 26036

East Asian (EAS) AF: 0.406 AC: 16087 AN: 39672

South Asian (SAS) AF: 0.280 AC: 24164 AN: 86194

European-Finnish (FIN) AF: 0.228 AC: 12139 AN: 53310

Middle Eastern (MID) AF: 0.326 AC: 1874 AN: 5752

European-Non Finnish (NFE) AF: 0.221 AC: 245087 AN: 1110724

Other (OTH) AF: 0.282 AC: 16985 AN: 60304

GnomAD4 genome AF: 0.368 AC: 55863 AN: 151960 Hom.: 12951 Cov.: 32 AF XY: 0.368 AC XY: 27353 AN XY: 74296

African (AFR) AF: 0.644 AC: 26679 AN: 41416

American (AMR) AF: 0.401 AC: 6125 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3458

East Asian (EAS) AF: 0.479 AC: 2466 AN: 5152

South Asian (SAS) AF: 0.297 AC: 1427 AN: 4808

European-Finnish (FIN) AF: 0.234 AC: 2476 AN: 10584

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15043 AN: 67968

Other (OTH) AF: 0.370 AC: 778 AN: 2102

Alfa AF: 0.280 Hom.: 1388

Bravo AF: 0.395

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.53
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6095; hg19: chr18-61558656; COSMIC: COSV55092615; COSMIC: COSV55092615;