NM_002639.5:c.568-2221C>G

Variant names:

• chr18-63496899-C-G
• rs1509478
• NM_002639.5:c.568-2221C>G

Variant summary

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

The NM_002639.5(SERPINB5):​c.568-2221C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 323,010 control chromosomes in the GnomAD database, including 49,630 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 0.53 (22582 hom., cov: 32)
  • Exomes 𝑓: 0.55 (27048 hom.)
• Consequence: SERPINB5 NM_002639.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 4 publications found

Genes affected

SERPINB5 (HGNC:8949): (serpin family B member 5) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ATP5MC1P6 (HGNC:39509): (ATP synthase membrane subunit c locus 1 pseudogene 6)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB5	NM_002639.5	c.568-2221C>G		intron_variant	Intron 5 of 6	ENST00000382771.9	NP_002630.2
SERPINB5	XM_006722483.4	c.55-2221C>G		intron_variant	Intron 2 of 3		XP_006722546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB5	ENST00000382771.9	c.568-2221C>G		intron_variant	Intron 5 of 6	1	NM_002639.5	ENSP00000372221.4
SERPINB5	ENST00000464346.1	n.250-2221C>G		intron_variant	Intron 2 of 3	3
SERPINB5	ENST00000465652.5	n.241-2221C>G		intron_variant	Intron 2 of 3	3
ATP5MC1P6	ENST00000451206.1	n.-90C>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81187 AN: 151902 Hom.: 22576 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.552 AC: 94315 AN: 170990 Hom.: 27048 AF XY: 0.532 AC XY: 51111 AN XY: 96034

African (AFR) AF: 0.373 AC: 1571 AN: 4216

American (AMR) AF: 0.510 AC: 4654 AN: 9130

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 2032 AN: 3538

East Asian (EAS) AF: 0.529 AC: 3705 AN: 7008

South Asian (SAS) AF: 0.384 AC: 13116 AN: 34186

European-Finnish (FIN) AF: 0.618 AC: 4847 AN: 7844

Middle Eastern (MID) AF: 0.528 AC: 316 AN: 598

European-Non Finnish (NFE) AF: 0.617 AC: 59295 AN: 96072

Other (OTH) AF: 0.569 AC: 4779 AN: 8398

GnomAD4 genome AF: 0.534 AC: 81217 AN: 152020 Hom.: 22582 Cov.: 32 AF XY: 0.531 AC XY: 39434 AN XY: 74324

African (AFR) AF: 0.380 AC: 15736 AN: 41464

American (AMR) AF: 0.531 AC: 8113 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2026 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2727 AN: 5172

South Asian (SAS) AF: 0.392 AC: 1887 AN: 4816

European-Finnish (FIN) AF: 0.613 AC: 6480 AN: 10566

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42468 AN: 67940

Other (OTH) AF: 0.542 AC: 1145 AN: 2114

Alfa AF: 0.573 Hom.: 3131

Bravo AF: 0.524

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.42
PhyloP100		1.3
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: rs1509478; hg19: chr18-61164132;