Genetic Variant CBLIF:c.*87G>A (chr11-59829397-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005142.3(CBLIF):c.*87G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 842,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CBLIF
NM_005142.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0950

Publications

0 publications found

Variant links:

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)

CBLIF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.*87G>A		3_prime_UTR	Exon 9 of 9	NP_005133.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CBLIF	ENST00000257248.3	TSL:1 MANE Select	c.*87G>A	3_prime_UTR	Exon 9 of 9	ENSP00000257248.2	P27352-1
CBLIF	ENST00000525058.5	TSL:2	n.*1308G>A	non_coding_transcript_exon	Exon 9 of 9	ENSP00000433196.1	E9PM21
CBLIF	ENST00000525058.5	TSL:2	n.*1308G>A	3_prime_UTR	Exon 9 of 9	ENSP00000433196.1	E9PM21

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

AN:

690684

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

AN XY:

370682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18714

American (AMR)

AF:

0.00

AC:

AN:

40966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20964

East Asian (EAS)

AF:

0.00

AC:

AN:

35426

South Asian (SAS)

AF:

0.000233

AC:

AN:

68704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4202

European-Non Finnish (NFE)

AF:

0.000178

AC:

AN:

415480

Other (OTH)

AF:

0.000173

AC:

AN:

34684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.0000718

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary intrinsic factor deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.4

(source)

DANN

Benign

0.63

PhyloP100

-0.095

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over