11-59831479-T-TTA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005142.3(CBLIF):c.1192+198_1192+199insTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 205,632 control chromosomes in the GnomAD database, including 385 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (385 hom., cov: 27)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 11-59831479-T-TTA is Benign according to our data. Variant chr11-59831479-T-TTA is described in ClinVar as [Benign]. Clinvar id is 1253162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBLIF	NM_005142.3	c.1192+198_1192+199insTA		intron_variant		ENST00000257248.3
CBLIF	XM_011544939.4	c.1150+198_1150+199insTA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBLIF	ENST00000257248.3	c.1192+198_1192+199insTA		intron_variant		1	NM_005142.3	P1
CBLIF	ENST00000525058.5	c.*1159+198_*1159+199insTA		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9216 AN: 146680 Hom.: 388 Cov.: 27

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0255

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0288

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0605

GnomAD4 exome AF: 0.0344 AC: 2025 AN: 58896 Hom.: 0 AF XY: 0.0364 AC XY: 1252 AN XY: 34422

Gnomad4 AFR exome AF: 0.0440

Gnomad4 AMR exome AF: 0.0731

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.0756

Gnomad4 SAS exome AF: 0.0290

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.0297

Gnomad4 OTH exome AF: 0.0313

GnomAD4 genome AF: 0.0628 AC: 9212 AN: 146736 Hom.: 385 Cov.: 27 AF XY: 0.0641 AC XY: 4578 AN XY: 71430

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0597

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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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;