rs770530971

Positions:

• chr11-59842516-GTTC-G
• chr11-59842516-GTTC-GTTCTTC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BS1 BS2

The NM_005142.3(CBLIF):​c.435_437del​(p.Lys145del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,614,012 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (3 hom.)
• Consequence: CBLIF NM_005142.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.39

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 -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005142.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 11-59842516-GTTC-G is Benign according to our data. Variant chr11-59842516-GTTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 208192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0016 (244/152346) while in subpopulation AMR AF= 0.0049 (75/15298). AF 95% confidence interval is 0.00401. There are 0 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLIF	NM_005142.3	c.435_437del	p.Lys145del	inframe_deletion	4/9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4	c.435_437del	p.Lys145del	inframe_deletion	4/9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3	c.435_437del	p.Lys145del	inframe_deletion	4/9	1	NM_005142.3	ENSP00000257248	P1
CBLIF	ENST00000532070.1	n.925_927del		non_coding_transcript_exon_variant	3/3	2
CBLIF	ENST00000525058.5	c.*402_*404del		3_prime_UTR_variant, NMD_transcript_variant	4/9	2		ENSP00000433196

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00128 AC: 321 AN: 251080 Hom.: 0 AF XY: 0.00127 AC XY: 172 AN XY: 135672

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00223

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00216 AC: 3151 AN: 1461666 Hom.: 3 AF XY: 0.00219 AC XY: 1594 AN XY: 727130

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00265

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00160 AC: 244 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.00158 AC XY: 118 AN XY: 74502

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00223

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000312 Hom.: 0

Bravo AF: 0.00145

EpiCase AF: 0.00196

EpiControl AF: 0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary intrinsic factor deficiency Benign:1 Other:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 05, 2024	- -
not provided, no classification provided	not provided	Inserm U 954, Faculté de Médecine de Nancy	-	- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs770530971; hg19: chr11-59609989;