rs6014573

Positions:

• chr20-56004403-C-A

Variant summary

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

The NM_080617.6(CBLN4):​c.-232G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 469,716 control chromosomes in the GnomAD database, including 28,780 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 0.39 (16102 hom., cov: 32)
  • Exomes 𝑓: 0.26 (12678 hom.)
• Consequence: CBLN4 NM_080617.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

Genes affected

CBLN4 (HGNC:16231): (cerebellin 4 precursor) This gene encodes a member of a family of small secreted proteins containing C1Q domains. Members of this family are involved in regulation of neurexin signalling during synapse development. The mouse homolog of the protein encoded by this gene competes with netrin to bind to the deleted in colorectal cancer receptor. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLN4	NM_080617.6	c.-232G>T		5_prime_UTR_variant	1/3	ENST00000064571.3	NP_542184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLN4	ENST00000064571.3	c.-232G>T		5_prime_UTR_variant	1/3	1	NM_080617.6	ENSP00000064571	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58644 AN: 151804 Hom.: 16055 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.256 AC: 81278 AN: 317794 Hom.: 12678 Cov.: 4 AF XY: 0.253 AC XY: 41569 AN XY: 164200

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.387 AC: 58747 AN: 151922 Hom.: 16102 Cov.: 32 AF XY: 0.387 AC XY: 28743 AN XY: 74264

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.305

Alfa AF: 0.239 Hom.: 7471

Bravo AF: 0.400

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.94

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: rs6014573; hg19: chr20-54579459;