rs11603020

chr11-57606859-T-Cchr11-57606859-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000062.3(SERPING1):c.1029+312T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 599,040 control chromosomes in the GnomAD database, including 17,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3924 hom., cov: 32)
  • Exomes 𝑓: 0.24 (13649 hom.)
• Consequence: SERPING1 NM_000062.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.502

Genes affected

SERPING1 (HGNC:1228): (serpin family G member 1) This gene encodes a highly glycosylated plasma protein involved in the regulation of the complement cascade. Its encoded protein, C1 inhibitor, inhibits activated C1r and C1s of the first complement component and thus regulates complement activation. It is synthesized in the liver, and its deficiency is associated with hereditary angioneurotic oedema (HANE). Alternative splicing results in multiple transcript variants encoding the same isoform. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-57606859-T-C is Benign according to our data. Variant chr11-57606859-T-C is described in ClinVar as [Benign]. Clinvar id is 983254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-57606859-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPING1	NM_000062.3	c.1029+312T>C		intron_variant		ENST00000278407.9
SERPING1	NM_001032295.2	c.1029+312T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPING1	ENST00000278407.9	c.1029+312T>C		intron_variant		1	NM_000062.3	P2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32255 AN: 152082 Hom.: 3924 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.239 AC: 106712 AN: 446840 Hom.: 13649 AF XY: 0.239 AC XY: 58370 AN XY: 244582

Gnomad4 AFR exome AF: 0.0988

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.0971

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.212 AC: 32255 AN: 152200 Hom.: 3924 Cov.: 32 AF XY: 0.213 AC XY: 15828 AN XY: 74426

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.232

Alfa AF: 0.229 Hom.: 2312

Bravo AF: 0.196

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Hereditary angioedema type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

CeMIA

-

This variant is considered likely benign or benign based on one or more of the following criteria: allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (BA1), allele frequency is greater than expected for disorder (BS1), it is observed in a healthy adult individual (BS2), it is predicted to be benign by multiple in silico algorithms (BP4), it is found in a case with an alternate molecular basis for the disease (BP5) and/or reputable source recently reports variant as benign (BP6). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.9
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11603020; hg19: chr11-57374332;