11-59831680-T-G

Variant names:

• chr11-59831680-T-G
• rs150005713
• NM_005142.3:c.1190A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005142.3(CBLIF):​c.1190A>C​(p.Glu397Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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, splice_region
• Scores: Splicing: ADA: 0.0004307
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.1190A>C	p.Glu397Ala	missense_variant, splice_region_variant	Exon 8 of 9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.1148A>C	p.Glu383Ala	missense_variant, splice_region_variant	Exon 8 of 9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3	c.1190A>C	p.Glu397Ala	missense_variant, splice_region_variant	Exon 8 of 9	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*1157A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 8 of 9	2		ENSP00000433196.1
CBLIF	ENST00000533067.1	n.237A>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
CBLIF	ENST00000525058.5	n.*1157A>C		3_prime_UTR_variant	Exon 8 of 9	2		ENSP00000433196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.063
Sift	Benign	0.051	T
Sift4G	Uncertain	0.027	D
Vest4		0.53
MutPred		0.38		Gain of catalytic residue at E397 (P = 0.2414);
MVP		0.36
MPC		0.14
ClinPred		0.64	D
GERP RS		4.3
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00043
dbscSNV1_RF	Benign	0.064
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs150005713; hg19: chr11-59599153;