11-57610519-G-T

Variant names:

• chr11-57610519-G-T
• rs2508443
• NM_000062.3:c.1030-1198G>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.1030-1198G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,074 control chromosomes in the GnomAD database, including 9,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9011 hom., cov: 32)
• Consequence: SERPING1 NM_000062.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.251
• Publications: 19 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=-0.89).
• BP6: Variant 11-57610519-G-T is Benign according to our data. Variant chr11-57610519-G-T is described in ClinVar as Benign. ClinVar VariationId is 983233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPING1	NM_000062.3	MANE Select	c.1030-1198G>T		intron	N/A	NP_000053.2
	SERPING1	NM_001032295.2		c.1030-1198G>T		intron	N/A	NP_001027466.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPING1	ENST00000278407.9	TSL:1 MANE Select	c.1030-1198G>T		intron	N/A	ENSP00000278407.4
	SERPING1	ENST00000619430.2	TSL:1	c.826-1198G>T		intron	N/A	ENSP00000478572.2
	SERPING1	ENST00000531133.5	TSL:1	n.*399-1198G>T		intron	N/A	ENSP00000435431.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50584 AN: 151956 Hom.: 9008 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.333 AC: 50612 AN: 152074 Hom.: 9011 Cov.: 32 AF XY: 0.328 AC XY: 24368 AN XY: 74348

African (AFR) AF: 0.237 AC: 9814 AN: 41484

American (AMR) AF: 0.319 AC: 4868 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3468

East Asian (EAS) AF: 0.130 AC: 674 AN: 5188

South Asian (SAS) AF: 0.341 AC: 1646 AN: 4824

European-Finnish (FIN) AF: 0.363 AC: 3829 AN: 10560

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27956 AN: 67972

Other (OTH) AF: 0.327 AC: 690 AN: 2108

Alfa AF: 0.368 Hom.: 28022

Bravo AF: 0.322

Asia WGS AF: 0.237 AC: 827 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary angioedema type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.75
DANN	Benign	0.46
PhyloP100		-0.25
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: rs2508443; hg19: chr11-57377992;