12-7062107-T-TA

Variant names:

• chr12-7062107-T-TA
• rs376183132
• NM_001734.5:c.5+204dupA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001734.5(C1S):​c.5+204dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 516,112 control chromosomes in the GnomAD database, including 2,018 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (2001 hom., cov: 27)
  • Exomes 𝑓: 0.092 (17 hom.)
• Consequence: C1S NM_001734.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

Genes affected

C1S (HGNC:1247): (complement C1s) This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-7062107-T-TA is Benign according to our data. Variant chr12-7062107-T-TA is described in ClinVar as [Benign]. Clinvar id is 1282313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1S	NM_001734.5	c.5+204dupA		intron_variant	Intron 2 of 11	ENST00000360817.10	NP_001725.1
C1S	NM_201442.4	c.5+204dupA		intron_variant	Intron 2 of 11		NP_958850.1
C1S	NM_001346850.2	c.-289+204dupA		intron_variant	Intron 2 of 10		NP_001333779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1S	ENST00000360817.10	c.5+204dupA		intron_variant	Intron 2 of 11	1	NM_001734.5	ENSP00000354057.5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 17420 AN: 141768 Hom.: 1997 Cov.: 27

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.0590

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0820

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.0920 AC: 34421 AN: 374280 Hom.: 17 Cov.: 0 AF XY: 0.0915 AC XY: 18424 AN XY: 201254

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.0731

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.0750

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0698

Gnomad4 NFE exome AF: 0.0838

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.123 AC: 17461 AN: 141832 Hom.: 2001 Cov.: 27 AF XY: 0.121 AC XY: 8340 AN XY: 68776

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0820

Gnomad4 EAS AF: 0.0615

Gnomad4 SAS AF: 0.0865

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0474

Gnomad4 OTH AF: 0.119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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: rs376183132; hg19: chr12-7169411;