11-59843998-G-C

Variant names:

• chr11-59843998-G-C
• NM_005142.3:c.137C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005142.3(CBLIF):​c.137C>G​(p.Ser46Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.137C>G	p.Ser46Trp	missense_variant	Exon 2 of 9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.137C>G	p.Ser46Trp	missense_variant	Exon 2 of 9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3	c.137C>G	p.Ser46Trp	missense_variant	Exon 2 of 9	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*104C>G		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000433196.1
CBLIF	ENST00000532070.1	n.183C>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
CBLIF	ENST00000525058.5	n.*104C>G		3_prime_UTR_variant	Exon 2 of 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

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.58	T
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Vest4		0.61
MutPred		0.75		Loss of disorder (P = 0.0039);
MVP		0.55
MPC		0.67
ClinPred		1.0	D
GERP RS		5.5
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-59611471;