11-59842516-GTTC-GTTCTTC

Position:

• chr11-59842516-GTTC-GTTCTTC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_005142.3(CBLIF):​c.435_437dupGAA​(p.Lys145dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBLIF NM_005142.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_005142.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.435_437dupGAA	p.Lys145dup	disruptive_inframe_insertion	4/9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.435_437dupGAA	p.Lys145dup	disruptive_inframe_insertion	4/9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3	c.435_437dupGAA	p.Lys145dup	disruptive_inframe_insertion	4/9	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*402_*404dupGAA		non_coding_transcript_exon_variant	4/9	2		ENSP00000433196.1
CBLIF	ENST00000532070.1	n.925_927dupGAA		non_coding_transcript_exon_variant	3/3	2
CBLIF	ENST00000525058.5	n.*402_*404dupGAA		3_prime_UTR_variant	4/9	2		ENSP00000433196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs770530971; hg19: chr11-59609989;