NM_016546.4:c.150G>A

Variant names:

• chr12-7108401-C-T
• rs200257444
• NM_016546.4:c.150G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016546.4(C1RL):​c.150G>A​(p.Gln50Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C1RL NM_016546.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 1 publications found

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-AS1 (HGNC:27461): (C1RL antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016546.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1RL	NM_016546.4	MANE Select	c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 6	NP_057630.2	Q9NZP8
	C1RL	NM_001297640.2		c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 5	NP_001284569.1
	C1RL	NM_001297642.2		c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 6	NP_001284571.1	F5GWF3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1RL	ENST00000266542.9	TSL:1 MANE Select	c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 6	ENSP00000266542.4	Q9NZP8
	C1RL	ENST00000544702.5	TSL:1	c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 6	ENSP00000441885.1	F5GWF3
	C1RL	ENST00000545337.1	TSL:1	c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 3	ENSP00000442611.1	F5H7C8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461698 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.76
PhyloP100		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200257444; hg19: chr12-7260997;