rs7100290

chr10-16903502-A-T

Variant summary

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

The NM_001081.4(CUBN):c.8062+464T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 151,964 control chromosomes in the GnomAD database, including 284 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 0.050 (284 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8062+464T>A		intron_variant		ENST00000377833.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8062+464T>A		intron_variant		1	NM_001081.4	P1
CUBN	ENST00000648092.1	n.598+464T>A		intron_variant, non_coding_transcript_variant
CUBN	ENST00000649933.1	n.424+464T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7629 AN: 151850 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0503 AC: 7646 AN: 151964 Hom.: 284 Cov.: 32 AF XY: 0.0488 AC XY: 3627 AN XY: 74328

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.0781

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0630 Hom.: 61

Bravo AF: 0.0465

Asia WGS AF: 0.0570 AC: 198 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	13
Dann	Benign	0.86

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: rs7100290; hg19: chr10-16945501;