11-59831741-C-A

Variant names:

• chr11-59831741-C-A
• NM_005142.3:c.1129G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005142.3(CBLIF):​c.1129G>T​(p.Ala377Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CBLIF NM_005142.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11348033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.1129G>T	p.Ala377Ser	missense_variant	Exon 8 of 9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.1087G>T	p.Ala363Ser	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.1129G>T	p.Ala377Ser	missense_variant	Exon 8 of 9	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*1096G>T		non_coding_transcript_exon_variant	Exon 8 of 9	2		ENSP00000433196.1
CBLIF	ENST00000533067.1	n.176G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
CBLIF	ENST00000525058.5	n.*1096G>T		3_prime_UTR_variant	Exon 8 of 9	2		ENSP00000433196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457270 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 725224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.1
DANN	Benign	0.94
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.042
Sift	Benign	0.28	T
Sift4G	Benign	0.53	T
Vest4		0.32
MutPred		0.29		Gain of disorder (P = 0.0155);
MVP		0.22
MPC		0.11
ClinPred		0.14	T
GERP RS		1.9
gMVP		0.49

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: chr11-59599214;