11-59831479-TTATATATATATATATA-TTATATATATATATATATATATA

Variant names:

• chr11-59831479-T-TTATATA
• rs3973727
• NM_005142.3:c.1192+193_1192+198dupTATATA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005142.3(CBLIF):​c.1192+193_1192+198dupTATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 60,642 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• 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.

• PM2: Very rare variant in population databases, with high coverage

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+193_1192+198dupTATATA		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+198_1192+199insTATATA		intron	N/A	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1159+198_*1159+199insTATATA		intron	N/A	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000533067.1	TSL:3	n.*51_*52insTATATA		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000660 AC: 4 AN: 60642 Hom.: 0 AF XY: 0.0000562 AC XY: 2 AN XY: 35556

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000509 AC: 1 AN: 1964

American (AMR) AF: 0.000402 AC: 1 AN: 2488

Ashkenazi Jewish (ASJ) AF: 0.000622 AC: 1 AN: 1608

East Asian (EAS) AF: 0.00 AC: 0 AN: 3648

South Asian (SAS) AF: 0.000388 AC: 1 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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 10

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.90

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;