11-59831479-TTATATATA-TTATA

Variant names:

• chr11-59831479-TTATA-T
• rs3973727
• NM_005142.3:c.1192+195_1192+198delTATA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_005142.3(CBLIF):​c.1192+195_1192+198delTATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 206,218 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 27)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0104 (619/59382) while in subpopulation AFR AF= 0.025 (48/1918). AF 95% confidence interval is 0.0194. There are 0 homozygotes in gnomad4_exome. There are 348 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.1192+195_1192+198delTATA		intron_variant	Intron 8 of 8	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.1150+195_1150+198delTATA		intron_variant	Intron 8 of 8		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3	c.1192+195_1192+198delTATA		intron_variant	Intron 8 of 8	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*1159+195_*1159+198delTATA		intron_variant	Intron 8 of 8	2		ENSP00000433196.1
CBLIF	ENST00000533067.1	n.*48_*51delTATA		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 17 AN: 146782 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0104 AC: 619 AN: 59382 Hom.: 0 AF XY: 0.00999 AC XY: 348 AN XY: 34836

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.00613

Gnomad4 ASJ exome AF: 0.00887

Gnomad4 EAS exome AF: 0.00670

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.00973

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.000123 AC: 18 AN: 146836 Hom.: 0 Cov.: 27 AF XY: 0.000140 AC XY: 10 AN XY: 71484

Gnomad4 AFR AF: 0.000395

Gnomad4 AMR AF: 0.0000686

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000216

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3973727; hg19: chr11-59598952;