18-63792182-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003784.4(SERPINB7):c.169-211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,184 control chromosomes in the GnomAD database, including 2,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (2182 hom., cov: 32)
• Consequence: SERPINB7 NM_003784.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-63792182-A-G is Benign according to our data. Variant chr18-63792182-A-G is described in ClinVar as [Benign]. Clinvar id is 1232822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB7	NM_003784.4	c.169-211A>G		intron_variant		ENST00000398019.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB7	ENST00000398019.7	c.169-211A>G		intron_variant		1	NM_003784.4	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19903 AN: 152066 Hom.: 2183 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.131 AC: 19920 AN: 152184 Hom.: 2182 Cov.: 32 AF XY: 0.131 AC XY: 9772 AN XY: 74404

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0931 Hom.: 197

Bravo AF: 0.146

Asia WGS AF: 0.284 AC: 985 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.6
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1720845; hg19: chr18-61459416;