11-59831479-TTATATATATATATATA-T

Variant names:

• chr11-59831479-TTATATATATATATATA-T
• rs3973727
• NM_005142.3:c.1192+183_1192+198delTATATATATATATATA

Variant summary

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

The NM_005142.3(CBLIF):​c.1192+183_1192+198delTATATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 60,642 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• 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 0 ACMG points.

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.1192+183_1192+198delTATATATATATATATA		intron	N/A	NP_005133.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	ENST00000257248.3	TSL:1 MANE Select	c.1192+183_1192+198delTATATATATATATATA		intron	N/A	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1159+183_*1159+198delTATATATATATATATA		intron	N/A	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000533067.1	TSL:3	n.*36_*51delTATATATATATATATA		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000165 AC: 1 AN: 60642 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 35556

African (AFR) AF: 0.00 AC: 0 AN: 1964

American (AMR) AF: 0.00 AC: 0 AN: 2488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1608

East Asian (EAS) AF: 0.000274 AC: 1 AN: 3648

South Asian (SAS) AF: 0.00 AC: 0 AN: 2578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42738

Other (OTH) AF: 0.00 AC: 0 AN: 3484

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs3973727; hg19: chr11-59598952;