rs1005511

Variant names:

• chr11-57599183-C-T
• rs1005511
• NM_000062.3:c.52-696C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000062.3(SERPING1):​c.52-696C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,878 control chromosomes in the GnomAD database, including 13,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (13101 hom., cov: 31)
• Consequence: SERPING1 NM_000062.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.398
• Publications: 18 publications found

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]

SERPING1 Gene-Disease associations (from GenCC):

• hereditary angioedema with C1Inh deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• C1 inhibitor deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary angioedema type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary angioedema type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 11-57599183-C-T is Benign according to our data. Variant chr11-57599183-C-T is described in ClinVar as Benign. ClinVar VariationId is 983238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPING1	NM_000062.3	c.52-696C>T		intron_variant	Intron 2 of 7	ENST00000278407.9	NP_000053.2
SERPING1	NM_001032295.2	c.52-696C>T		intron_variant	Intron 1 of 6		NP_001027466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPING1	ENST00000278407.9	c.52-696C>T		intron_variant	Intron 2 of 7	1	NM_000062.3	ENSP00000278407.4

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61080 AN: 151760 Hom.: 13081 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.403 AC: 61147 AN: 151878 Hom.: 13101 Cov.: 31 AF XY: 0.409 AC XY: 30349 AN XY: 74236

African (AFR) AF: 0.474 AC: 19618 AN: 41380

American (AMR) AF: 0.476 AC: 7266 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3885 AN: 5152

South Asian (SAS) AF: 0.458 AC: 2204 AN: 4808

European-Finnish (FIN) AF: 0.342 AC: 3605 AN: 10534

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21522 AN: 67950

Other (OTH) AF: 0.392 AC: 828 AN: 2112

Alfa AF: 0.354 Hom.: 40540

Bravo AF: 0.420

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary angioedema type 1 Benign:1

-

CeMIA

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.99
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-0.40
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: rs1005511; hg19: chr11-57366656;