NM_016546.4:c.*312G>A

Variant names:

• chr12-7096079-C-T
• rs3782928
• NM_016546.4:c.*312G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1RL	NM_016546.4	MANE Select	c.*312G>A		3_prime_UTR	Exon 6 of 6	NP_057630.2
	C1RL	NM_001297640.2		c.*312G>A		3_prime_UTR	Exon 5 of 5	NP_001284569.1
	C1RL	NM_001297642.2		c.*878G>A		3_prime_UTR	Exon 6 of 6	NP_001284571.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1RL	ENST00000266542.9	TSL:1 MANE Select	c.*312G>A		3_prime_UTR	Exon 6 of 6	ENSP00000266542.4
	C1RL	ENST00000545280.5	TSL:3	c.269-2209G>A		intron	N/A	ENSP00000438286.1
	C1RL	ENST00000504702.2	TSL:2	n.33-854G>A		intron	N/A

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

African (AFR) AF: 0.159 AC: 3160 AN: 19844

American (AMR) AF: 0.392 AC: 2182 AN: 5568

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 2967 AN: 9774

East Asian (EAS) AF: 0.153 AC: 1859 AN: 12118

South Asian (SAS) AF: 0.335 AC: 7344 AN: 21934

European-Finnish (FIN) AF: 0.207 AC: 1639 AN: 7918

Middle Eastern (MID) AF: 0.294 AC: 671 AN: 2286

European-Non Finnish (NFE) AF: 0.262 AC: 220163 AN: 840798

Other (OTH) AF: 0.254 AC: 9014 AN: 35476

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

African (AFR) AF: 0.169 AC: 7024 AN: 41444

American (AMR) AF: 0.367 AC: 5609 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1000 AN: 3466

East Asian (EAS) AF: 0.182 AC: 940 AN: 5158

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4816

European-Finnish (FIN) AF: 0.188 AC: 1989 AN: 10588

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 17987 AN: 67944

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.263 Hom.: 24024

Bravo AF: 0.250

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3782928; hg19: chr12-7248675;