10-16896272-T-G

Variant names:

• chr10-16896272-T-G
• rs77744173
• NM_001081.4:c.8598+2724A>C

Variant summary

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

The NM_001081.4(CUBN):​c.8598+2724A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 152,294 control chromosomes in the GnomAD database, including 528 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 0.077 (528 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8598+2724A>C		intron_variant	Intron 54 of 66	ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8598+2724A>C		intron_variant	Intron 54 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11782 AN: 152176 Hom.: 527 Cov.: 33

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0774 AC: 11781 AN: 152294 Hom.: 528 Cov.: 33 AF XY: 0.0759 AC XY: 5649 AN XY: 74474

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0437 Hom.: 44

Bravo AF: 0.0740

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.45

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: rs77744173; hg19: chr10-16938271;