rs558660

Variant names:

• chr11-59836421-A-G
• rs558660
• NM_005142.3:c.872-412T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-59836421-A-G
• chr11-59836421-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

CBLIF Gene-Disease associations (from GenCC):

• hereditary intrinsic factor deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.872-412T>C		intron_variant	Intron 6 of 8	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.830-412T>C		intron_variant	Intron 6 of 8		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3	c.872-412T>C		intron_variant	Intron 6 of 8	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*839-412T>C		intron_variant	Intron 6 of 8	2		ENSP00000433196.1
CBLIF	ENST00000533847.1	n.524-412T>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.962 AC: 39945 AN: 41538

American (AMR) AF: 0.884 AC: 13512 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2901 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3443 AN: 5174

South Asian (SAS) AF: 0.934 AC: 4506 AN: 4824

European-Finnish (FIN) AF: 0.837 AC: 8863 AN: 10592

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55879 AN: 68000

Other (OTH) AF: 0.860 AC: 1814 AN: 2110

Alfa AF: 0.844 Hom.: 59060

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs558660; hg19: chr11-59603894;