11-57599749-C-T

Variant names:

• chr11-57599749-C-T
• rs1005510
• NM_000062.3:c.52-130C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000062.3(SERPING1):​c.52-130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,287,044 control chromosomes in the GnomAD database, including 89,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12531 hom., cov: 31)
  • Exomes 𝑓: 0.35 (76959 hom.)
• Consequence: SERPING1 NM_000062.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.38
• Publications: 24 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, SD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-57599749-C-T is Benign according to our data. Variant chr11-57599749-C-T is described in ClinVar as Benign. ClinVar VariationId is 983239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000062.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPING1	NM_000062.3	MANE Select	c.52-130C>T		intron	N/A	NP_000053.2	P05155-1
	SERPING1	NM_001032295.2		c.52-130C>T		intron	N/A	NP_001027466.1	P05155-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPING1	ENST00000278407.9	TSL:1 MANE Select	c.52-130C>T		intron	N/A	ENSP00000278407.4	P05155-1
	SERPING1	ENST00000619430.2	TSL:1	c.52-130C>T		intron	N/A	ENSP00000478572.2	A0A087WUD9
	SERPING1	ENST00000531133.5	TSL:1	n.51+1428C>T		intron	N/A	ENSP00000435431.1	E9PK97

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59934 AN: 151838 Hom.: 12523 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.354 AC: 401906 AN: 1135086 Hom.: 76959 AF XY: 0.356 AC XY: 206031 AN XY: 578696

African (AFR) AF: 0.450 AC: 12146 AN: 26982

American (AMR) AF: 0.560 AC: 23032 AN: 41120

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 10664 AN: 23472

East Asian (EAS) AF: 0.761 AC: 28915 AN: 37972

South Asian (SAS) AF: 0.442 AC: 34458 AN: 77942

European-Finnish (FIN) AF: 0.330 AC: 14274 AN: 43236

Middle Eastern (MID) AF: 0.400 AC: 1963 AN: 4912

European-Non Finnish (NFE) AF: 0.310 AC: 257641 AN: 829830

Other (OTH) AF: 0.379 AC: 18813 AN: 49620

GnomAD4 genome AF: 0.395 AC: 59977 AN: 151958 Hom.: 12531 Cov.: 31 AF XY: 0.401 AC XY: 29778 AN XY: 74260

African (AFR) AF: 0.445 AC: 18422 AN: 41428

American (AMR) AF: 0.474 AC: 7230 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1587 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3886 AN: 5150

South Asian (SAS) AF: 0.453 AC: 2185 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3630 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21585 AN: 67968

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.361 Hom.: 30045

Bravo AF: 0.411

Asia WGS AF: 0.578 AC: 2008 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary angioedema type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.52
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1005510; hg19: chr11-57367222; COSMIC: COSV53543151; COSMIC: COSV53543151;