chr11-59831479-T-TTA

Variant names:

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

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+198dupTA 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
• 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-T-TTA is Benign according to our data. Variant chr11-59831479-T-TTA is described in ClinVar as Benign. ClinVar VariationId 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.

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+198dupTA		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+198_1192+199insTA		intron	N/A	ENSP00000257248.2	P27352-1
	CBLIF	ENST00000525058.5	TSL:2	n.*1159+198_*1159+199insTA		intron	N/A	ENSP00000433196.1	E9PM21
	CBLIF	ENST00000533067.1	TSL:3	n.*51_*52insTA		downstream_gene	N/A

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

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

African (AFR) AF: 0.0440 AC: 85 AN: 1930

American (AMR) AF: 0.0731 AC: 176 AN: 2408

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 40 AN: 1568

East Asian (EAS) AF: 0.0756 AC: 268 AN: 3546

South Asian (SAS) AF: 0.0290 AC: 72 AN: 2484

European-Finnish (FIN) AF: 0.0195 AC: 36 AN: 1842

Middle Eastern (MID) AF: 0.0444 AC: 11 AN: 248

European-Non Finnish (NFE) AF: 0.0297 AC: 1230 AN: 41454

Other (OTH) AF: 0.0313 AC: 107 AN: 3416

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

African (AFR) AF: 0.108 AC: 4363 AN: 40480

American (AMR) AF: 0.111 AC: 1612 AN: 14564

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 110 AN: 3406

East Asian (EAS) AF: 0.121 AC: 610 AN: 5036

South Asian (SAS) AF: 0.0466 AC: 216 AN: 4634

European-Finnish (FIN) AF: 0.0311 AC: 286 AN: 9190

Middle Eastern (MID) AF: 0.0280 AC: 8 AN: 286

European-Non Finnish (NFE) AF: 0.0281 AC: 1863 AN: 66212

Other (OTH) AF: 0.0597 AC: 121 AN: 2026

Alfa AF: 0.00716 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3973727; hg19: chr11-59598952;