rs558660

chr11-59836421-A-Gchr11-59836421-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005142.3(CBLIF):c.872-412T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,196 control chromosomes in the GnomAD database, including 57,475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57475 hom., cov: 32)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLIF	NM_005142.3	c.872-412T>C		intron_variant		ENST00000257248.3
CBLIF	XM_011544939.4	c.830-412T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLIF	ENST00000257248.3	c.872-412T>C		intron_variant		1	NM_005142.3	P1
CBLIF	ENST00000525058.5	c.*839-412T>C		intron_variant, NMD_transcript_variant		2
CBLIF	ENST00000533847.1	n.524-412T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131705 AN: 152078 Hom.: 57417 Cov.: 32

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.861

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.866 AC: 131823 AN: 152196 Hom.: 57475 Cov.: 32 AF XY: 0.866 AC XY: 64441 AN XY: 74408

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.860

Alfa AF: 0.839 Hom.: 30935

Bravo AF: 0.871

Asia WGS AF: 0.837 AC: 2911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.58
Dann	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs558660; hg19: chr11-59603894;