11-59831479-TTATATATATATATATA-TTATATATATATATA

Variant names:

• chr11-59831479-TTA-T
• rs3973727
• NM_005142.3:c.1192+197_1192+198delTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005142.3(CBLIF):​c.1192+197_1192+198delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 201,834 control chromosomes in the GnomAD database, including 1,895 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1792 hom., cov: 27)
  • Exomes 𝑓: 0.22 (103 hom.)
• Consequence: CBLIF NM_005142.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.898
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-59831479-TTA-T is Benign according to our data. Variant chr11-59831479-TTA-T is described in ClinVar as Benign. ClinVar VariationId is 1273950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005142.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	NM_005142.3	MANE Select	c.1192+197_1192+198delTA		intron	N/A	NP_005133.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	ENST00000257248.3	TSL:1 MANE Select	c.1192+197_1192+198delTA		intron	N/A	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1159+197_*1159+198delTA		intron	N/A	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000533067.1	TSL:3	n.*50_*51delTA		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17250 AN: 146450 Hom.: 1769 Cov.: 27

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0732

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.0518

Gnomad OTH AF: 0.0915

GnomAD4 exome AF: 0.222 AC: 12307 AN: 55332 Hom.: 103 AF XY: 0.221 AC XY: 7145 AN XY: 32366

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.300 AC: 567 AN: 1888

American (AMR) AF: 0.214 AC: 491 AN: 2290

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 294 AN: 1462

East Asian (EAS) AF: 0.179 AC: 602 AN: 3360

South Asian (SAS) AF: 0.248 AC: 573 AN: 2306

European-Finnish (FIN) AF: 0.255 AC: 448 AN: 1758

Middle Eastern (MID) AF: 0.184 AC: 43 AN: 234

European-Non Finnish (NFE) AF: 0.220 AC: 8555 AN: 38810

Other (OTH) AF: 0.228 AC: 734 AN: 3224

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.118 AC: 17312 AN: 146502 Hom.: 1792 Cov.: 27 AF XY: 0.118 AC XY: 8383 AN XY: 71306

African (AFR) AF: 0.279 AC: 11301 AN: 40470

American (AMR) AF: 0.0532 AC: 774 AN: 14558

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 100 AN: 3400

East Asian (EAS) AF: 0.0386 AC: 194 AN: 5030

South Asian (SAS) AF: 0.0363 AC: 168 AN: 4634

European-Finnish (FIN) AF: 0.119 AC: 1088 AN: 9110

Middle Eastern (MID) AF: 0.0524 AC: 15 AN: 286

European-Non Finnish (NFE) AF: 0.0518 AC: 3421 AN: 66092

Other (OTH) AF: 0.0916 AC: 185 AN: 2020

Alfa AF: 0.0168 Hom.: 10

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.90
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: rs3973727; hg19: chr11-59598952; COSMIC: COSV57238460; COSMIC: COSV57238460;