NM_002575.3:c.679-255A>C

Variant names:

• chr18-63902149-A-C
• rs1015416
• NM_002575.3:c.679-255A>C

Variant summary

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

The NM_002575.3(SERPINB2):​c.679-255A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,062 control chromosomes in the GnomAD database, including 13,485 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 (13485 hom., cov: 32)
• Consequence: SERPINB2 NM_002575.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 9 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]

ENSG00000289724 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	NM_002575.3	MANE Select	c.679-255A>C		intron	N/A	NP_002566.1	P05120
	SERPINB2	NM_001143818.2		c.679-255A>C		intron	N/A	NP_001137290.1	P05120

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB2	ENST00000299502.9	TSL:1 MANE Select	c.679-255A>C		intron	N/A	ENSP00000299502.4	P05120
	ENSG00000289724	ENST00000418725.1	TSL:5	c.307-255A>C		intron	N/A	ENSP00000392381.1	H7C004
	SERPINB2	ENST00000457692.5	TSL:5	c.679-255A>C		intron	N/A	ENSP00000401645.1	P05120

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56619 AN: 151944 Hom.: 13441 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.370

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56723 AN: 152062 Hom.: 13485 Cov.: 32 AF XY: 0.374 AC XY: 27770 AN XY: 74350

African (AFR) AF: 0.662 AC: 27444 AN: 41468

American (AMR) AF: 0.404 AC: 6162 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3472

East Asian (EAS) AF: 0.479 AC: 2470 AN: 5158

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2468 AN: 10586

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15073 AN: 67992

Other (OTH) AF: 0.375 AC: 790 AN: 2108

Alfa AF: 0.383 Hom.: 6211

Bravo AF: 0.401

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.48
PhyloP100		-0.37
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: rs1015416; hg19: chr18-61569383;