12-7062058-C-T

Position:

• chr12-7062058-C-T

Variant summary

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

The NM_001734.5(C1S):​c.5+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 835,256 control chromosomes in the GnomAD database, including 4,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2580 hom., cov: 30)
  • Exomes 𝑓: 0.054 (2032 hom.)
• Consequence: C1S NM_001734.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.985

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]

C1S (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-7062058-C-T is Benign according to our data. Variant chr12-7062058-C-T is described in ClinVar as [Benign]. Clinvar id is 1273754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1S	NM_001734.5	c.5+141C>T		intron_variant		ENST00000360817.10	NP_001725.1
C1S	NM_201442.4	c.5+141C>T		intron_variant			NP_958850.1
C1S	NM_001346850.2	c.-289+141C>T		intron_variant			NP_001333779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1S	ENST00000360817.10	c.5+141C>T		intron_variant		1	NM_001734.5	ENSP00000354057.5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19272 AN: 151110 Hom.: 2561 Cov.: 30

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0542 AC: 37108 AN: 684028 Hom.: 2032 Cov.: 9 AF XY: 0.0548 AC XY: 19971 AN XY: 364606

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.0485

Gnomad4 ASJ exome AF: 0.0819

Gnomad4 EAS exome AF: 0.0303

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.0226

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.0772

GnomAD4 genome AF: 0.128 AC: 19343 AN: 151228 Hom.: 2580 Cov.: 30 AF XY: 0.126 AC XY: 9287 AN XY: 73894

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.0841

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0938 Hom.: 185

Bravo AF: 0.141

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.56

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: rs12311345; hg19: chr12-7169362;