11-59829428-A-G

Variant names:

• chr11-59829428-A-G
• rs886048401
• NM_005142.3:c.*56T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005142.3(CBLIF):​c.*56T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 963,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CBLIF NM_005142.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.*56T>C		3_prime_UTR	Exon 9 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.*56T>C		3_prime_UTR	Exon 9 of 9	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1277T>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000525058.5	TSL:2	n.*1277T>C		3_prime_UTR	Exon 9 of 9	ENSP00000433196.1	E9PM21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 2 AN: 963982 Hom.: 0 Cov.: 13 AF XY: 0.00000399 AC XY: 2 AN XY: 501264

African (AFR) AF: 0.00 AC: 0 AN: 23998

American (AMR) AF: 0.00 AC: 0 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22972

East Asian (EAS) AF: 0.00 AC: 0 AN: 37500

South Asian (SAS) AF: 0.00 AC: 0 AN: 76236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4798

European-Non Finnish (NFE) AF: 0.00000304 AC: 2 AN: 657492

Other (OTH) AF: 0.00 AC: 0 AN: 44026

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		0.25

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: rs886048401; hg19: chr11-59596901;