rs6014573

Variant names:

• chr20-56004403-C-A
• rs6014573
• NM_080617.6:c.-232G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080617.6. 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
	CBLN4	NM_080617.6	MANE Select	c.-232G>T		5_prime_UTR	Exon 1 of 3	NP_542184.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLN4	ENST00000064571.3	TSL:1 MANE Select	c.-232G>T		5_prime_UTR	Exon 1 of 3	ENSP00000064571.2

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

African (AFR) AF: 0.766 AC: 5448 AN: 7108

American (AMR) AF: 0.238 AC: 1840 AN: 7734

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 1613 AN: 10228

East Asian (EAS) AF: 0.505 AC: 11424 AN: 22622

South Asian (SAS) AF: 0.313 AC: 5491 AN: 17568

European-Finnish (FIN) AF: 0.298 AC: 7759 AN: 26038

Middle Eastern (MID) AF: 0.209 AC: 323 AN: 1542

European-Non Finnish (NFE) AF: 0.204 AC: 41892 AN: 204986

Other (OTH) AF: 0.275 AC: 5488 AN: 19968

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

African (AFR) AF: 0.776 AC: 32157 AN: 41424

American (AMR) AF: 0.238 AC: 3630 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3464

East Asian (EAS) AF: 0.499 AC: 2552 AN: 5116

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4808

European-Finnish (FIN) AF: 0.291 AC: 3078 AN: 10576

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.210 AC: 14235 AN: 67946

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.253 Hom.: 11121

Bravo AF: 0.400

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		1.4
Mutation Taster		=300/0	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: rs6014573; hg19: chr20-54579459;