11-59831479-TTATATATATATATATA-TTATATATATATA

Variant names:

• chr11-59831479-TTATA-T
• rs3973727
• NM_005142.3:c.1192+195_1192+198delTATA

Variant summary

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

The NM_005142.3(CBLIF):​c.1192+195_1192+198delTATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 206,218 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: 𝑓 0.00012 (0 hom., cov: 27)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• 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+195_1192+198delTATA		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+195_1192+198delTATA		intron	N/A	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1159+195_*1159+198delTATA		intron	N/A	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000533067.1	TSL:3	n.*48_*51delTATA		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 17 AN: 146782 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0104 AC: 619 AN: 59382 Hom.: 0 AF XY: 0.00999 AC XY: 348 AN XY: 34836

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

African (AFR) AF: 0.0250 AC: 48 AN: 1918

American (AMR) AF: 0.00613 AC: 15 AN: 2448

Ashkenazi Jewish (ASJ) AF: 0.00887 AC: 14 AN: 1578

East Asian (EAS) AF: 0.00670 AC: 24 AN: 3580

South Asian (SAS) AF: 0.0120 AC: 30 AN: 2504

European-Finnish (FIN) AF: 0.0178 AC: 33 AN: 1850

Middle Eastern (MID) AF: 0.00794 AC: 2 AN: 252

European-Non Finnish (NFE) AF: 0.00973 AC: 407 AN: 41840

Other (OTH) AF: 0.0135 AC: 46 AN: 3412

⚠️ 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 AF: 0.000123 AC: 18 AN: 146836 Hom.: 0 Cov.: 27 AF XY: 0.000140 AC XY: 10 AN XY: 71484

African (AFR) AF: 0.000395 AC: 16 AN: 40516

American (AMR) AF: 0.0000686 AC: 1 AN: 14578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 5036

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66250

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.00 Hom.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

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

Other links and lift over

dbSNP: rs3973727; hg19: chr11-59598952;