Genetic Variant CBLIF:c.1074-3delT (chr11-59831798-TA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005142.3(CBLIF):c.1074-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000724 in 1,298,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 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)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

CBLIF
NM_005142.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 link	c.1074-3delT		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000257248.3	NP_005133.2	P27352-1
CBLIF	XM_011544939.4 link	c.1032-3delT		splice_region_variant, intron_variant	Intron 7 of 8		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CBLIF	ENST00000257248.3 link	c.1074-3delT	splice_region_variant, intron_variant	Intron 7 of 8	1	NM_005142.3	ENSP00000257248.2	P27352-1
CBLIF	ENST00000525058.5 link	n.*1041-3delT	splice_region_variant, intron_variant	Intron 7 of 8	2		ENSP00000433196.1	E9PM21
CBLIF	ENST00000533067.1 link	n.121-3delT	splice_region_variant, intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251032

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000724

AC:

AN:

1298670

Hom.:

Cov.:

AF XY:

0.0000657

AC XY:

AN XY:

654664

show subpopulations

Gnomad4 AFR exome

AF:

0.0000330

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000945

Gnomad4 OTH exome

AF:

0.0000182

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over