NM_005142.3:c.1169delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC

Variant names:

• chr11-59831701-C-GGGGAGGGGGGGGTTTGGTGGAAATTTTTTGTTATGATGTCTGTGTGGAAAGCGGCTGTG
• NM_005142.3:c.1169delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_005142.3(CBLIF):​c.1169delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC​(p.Ser390ThrfsTer10) variant causes a frameshift, stop gained, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBLIF NM_005142.3 frameshift, stop_gained, missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• Publications: 0 publications found

Genes affected

CBLIF (HGNC:4268): (cobalamin binding intrinsic factor) This gene is a member of the cobalamin transport protein family. It encodes a glycoprotein secreted by parietal cells of the gastric mucosa and is required for adequate absorption of vitamin B12. Vitamin B12 is necessary for erythrocyte maturation and mutations in this gene may lead to congenital pernicious anemia. [provided by RefSeq, Jul 2008]

CBLIF Gene-Disease associations (from GenCC):

• hereditary intrinsic factor deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0678 CDS is truncated, and there are 1 pathogenic variants in the truncated region.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005142.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	NM_005142.3	MANE Select	c.1169delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC	p.Ser390ThrfsTer10	frameshift stop_gained missense	Exon 8 of 9	NP_005133.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	ENST00000257248.3	TSL:1 MANE Select	c.1169delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC	p.Ser390ThrfsTer10	frameshift stop_gained missense	Exon 8 of 9	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1136delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC		non_coding_transcript_exon	Exon 8 of 9	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000533067.1	TSL:3	n.216delGinsCACAGCCGCTTTCCACACAGACATCATAACAAAAAATTTCCACCAAACCCCCCCCTCCCC		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary intrinsic factor deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-59599174;