12-7096079-C-T

Position:

• chr12-7096079-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016546.4(C1RL):​c.*312G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,107,724 control chromosomes in the GnomAD database, including 37,929 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4892 hom., cov: 32)
  • Exomes 𝑓: 0.26 (33037 hom.)
• Consequence: C1RL NM_016546.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

Genes affected

C1RL (HGNC:21265): (complement C1r subcomponent like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

C1RL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1RL	NM_016546.4	c.*312G>A		3_prime_UTR_variant	6/6	ENST00000266542.9	NP_057630.2
C1RL	NM_001297640.2	c.*312G>A		3_prime_UTR_variant	5/5		NP_001284569.1
C1RL	NM_001297642.2	c.*878G>A		3_prime_UTR_variant	6/6		NP_001284571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1RL	ENST00000266542	c.*312G>A		3_prime_UTR_variant	6/6	1	NM_016546.4	ENSP00000266542.4
C1RL	ENST00000545280.5	c.269-2209G>A		intron_variant		3		ENSP00000438286.1
C1RL	ENST00000504702.2	n.33-854G>A		intron_variant		2
C1RL	ENST00000539803.5	n.134-2209G>A		intron_variant		5		ENSP00000444157.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37056 AN: 151888 Hom.: 4886 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.261 AC: 248999 AN: 955716 Hom.: 33037 Cov.: 31 AF XY: 0.262 AC XY: 117109 AN XY: 446858

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.244 AC: 37090 AN: 152008 Hom.: 4892 Cov.: 32 AF XY: 0.242 AC XY: 18011 AN XY: 74300

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.246

Alfa AF: 0.266 Hom.: 11617

Bravo AF: 0.250

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.55

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: rs3782928; hg19: chr12-7248675;