11-59831783-T-G

Variant names:

• chr11-59831783-T-G
• rs760298108
• NM_005142.3:c.1087A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005142.3(CBLIF):​c.1087A>C​(p.Met363Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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)
• Consequence: CBLIF NM_005142.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27708954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.1087A>C	p.Met363Leu	missense_variant	Exon 8 of 9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.1045A>C	p.Met349Leu	missense_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.1087A>C	p.Met363Leu	missense_variant	Exon 8 of 9	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*1054A>C		non_coding_transcript_exon_variant	Exon 8 of 9	2		ENSP00000433196.1
CBLIF	ENST00000533067.1	n.134A>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
CBLIF	ENST00000525058.5	n.*1054A>C		3_prime_UTR_variant	Exon 8 of 9	2		ENSP00000433196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

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	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.95
Eigen	Benign	-0.10
Eigen_PC	Benign	0.0029
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.96	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.094
Sift	Benign	0.10	T
Sift4G	Benign	0.24	T
Vest4		0.49
MutPred		0.33		Loss of loop (P = 0.1242);
MVP		0.35
MPC		0.12
ClinPred		0.42	T
GERP RS		4.2
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs760298108; hg19: chr11-59599256;