12-7062270-C-CAAAAA

Variant names:

• chr12-7062270-C-CAAAAA
• rs373096669
• NM_001734.5:c.6-193_6-189dupAAAAA

Variant summary

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

The NM_001734.5(C1S):​c.6-193_6-189dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1980 hom., cov: 17)
  • Exomes 𝑓: 0.052 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1S NM_001734.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

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 12-7062270-C-CAAAAA is Benign according to our data. Variant chr12-7062270-C-CAAAAA is described in ClinVar as [Benign]. Clinvar id is 1247086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1S	NM_001734.5	c.6-193_6-189dupAAAAA		intron_variant	Intron 2 of 11	ENST00000360817.10	NP_001725.1
C1S	NM_201442.4	c.6-193_6-189dupAAAAA		intron_variant	Intron 2 of 11		NP_958850.1
C1S	NM_001346850.2	c.-289+365_-289+369dupAAAAA		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.6-205_6-204insAAAAA		intron_variant	Intron 2 of 11	1	NM_001734.5	ENSP00000354057.5

Frequencies

GnomAD3 genomes AF: 0.161 AC: 17210 AN: 107172 Hom.: 1978 Cov.: 17

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0843

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0518 AC: 17007 AN: 328544 Hom.: 8 Cov.: 0 AF XY: 0.0516 AC XY: 9157 AN XY: 177624

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0509

Gnomad4 ASJ exome AF: 0.0521

Gnomad4 EAS exome AF: 0.0272

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.0380

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0553

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.161 AC: 17213 AN: 107176 Hom.: 1980 Cov.: 17 AF XY: 0.158 AC XY: 7965 AN XY: 50394

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.150

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs373096669; hg19: chr12-7169574;