rs904804054

Variant names:

• chr5-179678771-G-A
• rs904804054
• NM_001164444.2:c.541C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-179678771-G-A
• chr5-179678771-G-C
• chr5-179678771-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001164444.2(CBY3):​c.541C>T​(p.Leu181Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: CBY3 NM_001164444.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

Genes affected

CBY3 (HGNC:33278): (chibby family member 3)

CANX (HGNC:1473): (calnexin) This gene encodes a member of the calnexin family of molecular chaperones. The encoded protein is a calcium-binding, endoplasmic reticulum (ER)-associated protein that interacts transiently with newly synthesized N-linked glycoproteins, facilitating protein folding and assembly. It may also play a central role in the quality control of protein folding by retaining incorrectly folded protein subunits within the ER for degradation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.73 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBY3	NM_001164444.2	c.541C>T	p.Leu181Leu	synonymous_variant	Exon 2 of 2	ENST00000376974.5	NP_001157916.1
CBY3	XM_047417524.1	c.250C>T	p.Leu84Leu	synonymous_variant	Exon 2 of 2		XP_047273480.1
CANX	XM_011534665.4	c.-10G>A		5_prime_UTR_variant	Exon 1 of 15		XP_011532967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBY3	ENST00000376974.5	c.541C>T	p.Leu181Leu	synonymous_variant	Exon 2 of 2	2	NM_001164444.2	ENSP00000366173.4
CANX	ENST00000681674	c.-10G>A		5_prime_UTR_variant	Exon 1 of 15			ENSP00000505013.1
CANX	ENST00000681712	c.-559G>A		5_prime_UTR_variant	Exon 1 of 16			ENSP00000506061.1
CANX	ENST00000681903	c.-517G>A		5_prime_UTR_variant	Exon 1 of 15			ENSP00000506509.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000701 AC: 1 AN: 142718 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000146

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.1
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: rs904804054; hg19: chr5-179105772;