18-63793052-A-T

Position:

• chr18-63793052-A-T

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.220-109A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 502,618 control chromosomes in the GnomAD database, including 4,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1883 hom., cov: 32)
  • Exomes 𝑓: 0.090 (2843 hom.)
• Consequence: SERPINB7 NM_003784.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.263

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=-0.96).
• BP6: Variant 18-63793052-A-T is Benign according to our data. Variant chr18-63793052-A-T is described in ClinVar as [Benign]. Clinvar id is 1235353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB7	NM_003784.4	c.220-109A>T		intron_variant		ENST00000398019.7	NP_003775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB7	ENST00000398019.7	c.220-109A>T		intron_variant		1	NM_003784.4	ENSP00000381101.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18553 AN: 152130 Hom.: 1885 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0901 AC: 31560 AN: 350370 Hom.: 2843 AF XY: 0.0907 AC XY: 16688 AN XY: 183938

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0533

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.0298

Gnomad4 NFE exome AF: 0.0539

Gnomad4 OTH exome AF: 0.0997

GnomAD4 genome AF: 0.122 AC: 18568 AN: 152248 Hom.: 1883 Cov.: 32 AF XY: 0.123 AC XY: 9139 AN XY: 74448

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0252

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0305 Hom.: 22

Bravo AF: 0.136

Asia WGS AF: 0.283 AC: 979 AN: 3464

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	-0.96
CADD	Benign	0.71
DANN	Benign	0.39

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: rs1701631; hg19: chr18-61460286;