rs7070148

Variant names:

• chr10-17122626-A-C
• rs7070148
• NM_001081.4:c.593+169T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-17122626-A-C
• chr10-17122626-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001081.4(CUBN):​c.593+169T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 653,454 control chromosomes in the GnomAD database, including 3,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (512 hom., cov: 32)
  • Exomes 𝑓: 0.095 (3064 hom.)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.180

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-17122626-A-C is Benign according to our data. Variant chr10-17122626-A-C is described in ClinVar as [Benign]. Clinvar id is 1286315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.593+169T>G		intron_variant	Intron 6 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.593+169T>G		intron_variant	Intron 6 of 54		XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.593+169T>G		intron_variant	Intron 6 of 66	1	NM_001081.4	ENSP00000367064.4
CUBN	ENST00000433666.5	c.255-41T>G		intron_variant	Intron 4 of 4	5		ENSP00000415970.1

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10177 AN: 152126 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.0684

GnomAD2 exomes AF: 0.0916 AC: 10693 AN: 116756 AF XY: 0.101

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0423

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0213

Gnomad FIN exome AF: 0.0890

Gnomad NFE exome AF: 0.0878

Gnomad OTH exome AF: 0.0806

GnomAD4 exome AF: 0.0947 AC: 47489 AN: 501210 Hom.: 3064 Cov.: 3 AF XY: 0.103 AC XY: 28172 AN XY: 272392

Gnomad4 AFR exome AF: 0.0203 AC: 264 AN: 13000

Gnomad4 AMR exome AF: 0.0416 AC: 1037 AN: 24938

Gnomad4 ASJ exome AF: 0.111 AC: 1856 AN: 16668

Gnomad4 EAS exome AF: 0.0207 AC: 608 AN: 29430

Gnomad4 SAS exome AF: 0.223 AC: 12304 AN: 55146

Gnomad4 FIN exome AF: 0.0890 AC: 3859 AN: 43380

Gnomad4 NFE exome AF: 0.0862 AC: 24825 AN: 287828

Gnomad4 Remaining exome AF: 0.0860 AC: 2333 AN: 27130

GnomAD4 genome AF: 0.0668 AC: 10174 AN: 152244 Hom.: 512 Cov.: 32 AF XY: 0.0703 AC XY: 5230 AN XY: 74426

Gnomad4 AFR AF: 0.0198 AC: 0.0198113 AN: 0.0198113

Gnomad4 AMR AF: 0.0476 AC: 0.0475693 AN: 0.0475693

Gnomad4 ASJ AF: 0.114 AC: 0.114187 AN: 0.114187

Gnomad4 EAS AF: 0.0243 AC: 0.0243056 AN: 0.0243056

Gnomad4 SAS AF: 0.239 AC: 0.239419 AN: 0.239419

Gnomad4 FIN AF: 0.0907 AC: 0.0906775 AN: 0.0906775

Gnomad4 NFE AF: 0.0831 AC: 0.0830613 AN: 0.0830613

Gnomad4 OTH AF: 0.0705 AC: 0.0705492 AN: 0.0705492

Alfa AF: 0.0731 Hom.: 426

Bravo AF: 0.0569

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.58
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs7070148; hg19: chr10-17164625; COSMIC: COSV64701242; COSMIC: COSV64701242;