rs2867802

Variant names:

• chr11-59835891-G-A
• rs2867802
• NM_005142.3:c.990C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-59835891-G-A
• chr11-59835891-G-C
• chr11-59835891-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005142.3(CBLIF):​c.990C>T​(p.Asn330Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,614,002 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (497 hom.)
• Consequence: CBLIF NM_005142.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.848
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-59835891-G-A is Benign according to our data. Variant chr11-59835891-G-A is described in ClinVar as Benign. ClinVar VariationId is 305031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.848 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.064 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	NM_005142.3	MANE Select	c.990C>T	p.Asn330Asn	synonymous	Exon 7 of 9	NP_005133.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBLIF	ENST00000257248.3	TSL:1 MANE Select	c.990C>T	p.Asn330Asn	synonymous	Exon 7 of 9	ENSP00000257248.2
	CBLIF	ENST00000525058.5	TSL:2	n.*957C>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000433196.1
	CBLIF	ENST00000533067.1	TSL:3	n.37C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1560 AN: 152142 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.0216 AC: 5432 AN: 251384 AF XY: 0.0166

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.0552

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000528

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.00652 AC: 9528 AN: 1461742 Hom.: 497 Cov.: 32 AF XY: 0.00577 AC XY: 4197 AN XY: 727170

African (AFR) AF: 0.00122 AC: 41 AN: 33478

American (AMR) AF: 0.113 AC: 5039 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00371 AC: 97 AN: 26134

East Asian (EAS) AF: 0.0737 AC: 2925 AN: 39700

South Asian (SAS) AF: 0.00384 AC: 331 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000588 AC: 654 AN: 1111868

Other (OTH) AF: 0.00722 AC: 436 AN: 60392

GnomAD4 genome AF: 0.0102 AC: 1557 AN: 152260 Hom.: 51 Cov.: 32 AF XY: 0.0113 AC XY: 839 AN XY: 74438

African (AFR) AF: 0.00221 AC: 92 AN: 41554

American (AMR) AF: 0.0674 AC: 1031 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.0593 AC: 307 AN: 5174

South Asian (SAS) AF: 0.00727 AC: 35 AN: 4812

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68032

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00794 Hom.: 47

Bravo AF: 0.0158

Asia WGS AF: 0.0470 AC: 163 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000652

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary intrinsic factor deficiency (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.41
DANN	Benign	0.47
PhyloP100		-0.85
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: rs2867802; hg19: chr11-59603364; COSMIC: COSV57238365;