chr18-63791454-C-G

Variant names:

• chr18-63791454-C-G
• rs1720843
• NM_003784.4:c.169-939C>G

Variant summary

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

The NM_003784.4(SERPINB7):​c.169-939C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,840 control chromosomes in the GnomAD database, including 3,605 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 0.17 (3605 hom., cov: 32)
• Consequence: SERPINB7 NM_003784.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 5 publications found

Genes affected

SERPINB7 (HGNC:13902): (serpin family B member 7) This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

SERPINB7 Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, Nagashima type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

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 (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003784.4. 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
	SERPINB7	NM_003784.4	MANE Select	c.169-939C>G		intron	N/A	NP_003775.1
	SERPINB7	NM_001040147.3		c.169-939C>G		intron	N/A	NP_001035237.1
	SERPINB7	NM_001261830.2		c.169-939C>G		intron	N/A	NP_001248759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB7	ENST00000398019.7	TSL:1 MANE Select	c.169-939C>G		intron	N/A	ENSP00000381101.2
	SERPINB7	ENST00000336429.6	TSL:1	c.169-939C>G		intron	N/A	ENSP00000337212.2
	SERPINB7	ENST00000546027.5	TSL:2	c.169-939C>G		intron	N/A	ENSP00000444861.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26286 AN: 151722 Hom.: 3598 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0849

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.173 AC: 26319 AN: 151840 Hom.: 3605 Cov.: 32 AF XY: 0.174 AC XY: 12932 AN XY: 74186

African (AFR) AF: 0.339 AC: 14033 AN: 41346

American (AMR) AF: 0.149 AC: 2283 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0849 AC: 294 AN: 3462

East Asian (EAS) AF: 0.500 AC: 2578 AN: 5154

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4824

European-Finnish (FIN) AF: 0.0414 AC: 436 AN: 10526

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5132 AN: 67940

Other (OTH) AF: 0.181 AC: 381 AN: 2110

Alfa AF: 0.0230 Hom.: 12

Bravo AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.036
DANN	Benign	0.37
PhyloP100		-1.7
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: rs1720843; hg19: chr18-61458688;