11-59831479-TTATATATA-TTATATATATATA

Variant names:

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

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+198dupTATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 207,476 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 27)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898

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 amr. gnomad4 allele frequency = 0.00194 (285/146868) while in subpopulation AMR AF= 0.0059 (86/14578). AF 95% confidence interval is 0.00489. There are 1 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 27. 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+198dupTATA		intron_variant	Intron 8 of 8	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.1150+195_1150+198dupTATA		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+198_1192+199insTATA		intron_variant	Intron 8 of 8	1	NM_005142.3	ENSP00000257248.2
CBLIF	ENST00000525058.5	n.*1159+198_*1159+199insTATA		intron_variant	Intron 8 of 8	2		ENSP00000433196.1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 285 AN: 146812 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00352

Gnomad EAS AF: 0.00237

Gnomad SAS AF: 0.00129

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000302

Gnomad OTH AF: 0.00297

GnomAD4 exome AF: 0.000412 AC: 25 AN: 60608 Hom.: 0 AF XY: 0.000338 AC XY: 12 AN XY: 35532

Gnomad4 AFR exome AF: 0.000510

Gnomad4 AMR exome AF: 0.000805

Gnomad4 ASJ exome AF: 0.000623

Gnomad4 EAS exome AF: 0.00165

Gnomad4 SAS exome AF: 0.000389

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000211

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00194 AC: 285 AN: 146868 Hom.: 1 Cov.: 27 AF XY: 0.00190 AC XY: 136 AN XY: 71512

Gnomad4 AFR AF: 0.00353

Gnomad4 AMR AF: 0.00590

Gnomad4 ASJ AF: 0.00352

Gnomad4 EAS AF: 0.00238

Gnomad4 SAS AF: 0.00129

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000302

Gnomad4 OTH AF: 0.00296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;