rs2796835

chr10-16901372-G-Achr10-16901372-G-Cchr10-16901372-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001081.4(CUBN):c.8150C>T(p.Ser2717Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2717W) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CUBN NM_001081.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09

Genes affected

CUBN (HGNC:2548): (cubilin) Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22304183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8150C>T	p.Ser2717Leu	missense_variant	52/67	ENST00000377833.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8150C>T	p.Ser2717Leu	missense_variant	52/67	1	NM_001081.4	P1
CUBN	ENST00000649933.1	n.512C>T		non_coding_transcript_exon_variant	4/5
CUBN	ENST00000648092.1			downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 53 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	0.97	N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.099
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.55		Loss of disorder (P = 0.0212);
MVP		0.52
MPC		0.070
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.10
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2796835; hg19: chr10-16943371;