ENST00000336429.6:c.-19+4331G>T

Variant names:

• chr18-63757451-G-T
• rs1106320
• ENST00000336429.6:c.-19+4331G>T

Variant summary

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

The ENST00000336429.6(SERPINB7):​c.-19+4331G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,282 control chromosomes in the GnomAD database, including 127 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 0.033 (127 hom., cov: 32)
• Consequence: SERPINB7 ENST00000336429.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB7	NM_001040147.3	c.-19+4331G>T		intron_variant	Intron 1 of 7		NP_001035237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB7	ENST00000336429.6	c.-19+4331G>T		intron_variant	Intron 1 of 7	1		ENSP00000337212.2
SERPINB7	ENST00000425392.5	c.-19+4331G>T		intron_variant	Intron 1 of 4	3		ENSP00000397301.1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4985 AN: 152164 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0327 AC: 4987 AN: 152282 Hom.: 127 Cov.: 32 AF XY: 0.0320 AC XY: 2384 AN XY: 74452

African (AFR) AF: 0.0661 AC: 2745 AN: 41550

American (AMR) AF: 0.0204 AC: 313 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5184

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4822

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1382 AN: 68018

Other (OTH) AF: 0.0359 AC: 76 AN: 2116

Alfa AF: 0.0209 Hom.: 16

Bravo AF: 0.0342

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.60
PhyloP100		-0.20
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: rs1106320; hg19: chr18-61424685;