chr12-7062357-C-T

Position:

• chr12-7062357-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001734.5(C1S):​c.6-118C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 769,064 control chromosomes in the GnomAD database, including 6,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1280 hom., cov: 31)
  • Exomes 𝑓: 0.13 (5715 hom.)
• Consequence: C1S NM_001734.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.593

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-7062357-C-T is Benign according to our data. Variant chr12-7062357-C-T is described in ClinVar as [Benign]. Clinvar id is 1277281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1S	NM_001734.5	c.6-118C>T		intron_variant		ENST00000360817.10	NP_001725.1
C1S	NM_201442.4	c.6-118C>T		intron_variant			NP_958850.1
C1S	NM_001346850.2	c.-289+440C>T		intron_variant			NP_001333779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1S	ENST00000360817.10	c.6-118C>T		intron_variant		1	NM_001734.5	ENSP00000354057.5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19637 AN: 151666 Hom.: 1274 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.130 AC: 80549 AN: 617282 Hom.: 5715 Cov.: 8 AF XY: 0.129 AC XY: 42747 AN XY: 331756

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0762

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.0884

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.129 AC: 19649 AN: 151782 Hom.: 1280 Cov.: 31 AF XY: 0.128 AC XY: 9467 AN XY: 74164

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0931

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0875

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.117

Alfa AF: 0.141 Hom.: 1144

Bravo AF: 0.121

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.81
CADD	Benign	1.6
DANN	Benign	0.79

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: rs11064497; hg19: chr12-7169661;