rs526934

Variant names:

• chr11-59866020-G-A
• rs526934
• NM_001062.4:c.79+372C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001062.4(TCN1):​c.79+372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,088 control chromosomes in the GnomAD database, including 45,494 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45494 hom., cov: 32)
• Consequence: TCN1 NM_001062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 37 publications found

Genes affected

TCN1 (HGNC:11652): (transcobalamin 1) This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This protein is a major constituent of secondary granules in neutrophils and facilitates the transport of cobalamin into cells. [provided by RefSeq, Jul 2008]

TCN1 Gene-Disease associations (from GenCC):

• transcobalamin I deficiency

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001062.4. 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
	TCN1	NM_001062.4	MANE Select	c.79+372C>T		intron	N/A	NP_001053.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCN1	ENST00000257264.4	TSL:1 MANE Select	c.79+372C>T		intron	N/A	ENSP00000257264.3	P20061
	TCN1	ENST00000532419.5	TSL:5	n.98+372C>T		intron	N/A
	TCN1	ENST00000534531.1	TSL:5	n.80+372C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117206 AN: 151970 Hom.: 45441 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.771 AC: 117320 AN: 152088 Hom.: 45494 Cov.: 32 AF XY: 0.776 AC XY: 57680 AN XY: 74366

African (AFR) AF: 0.856 AC: 35545 AN: 41510

American (AMR) AF: 0.771 AC: 11762 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3472

East Asian (EAS) AF: 0.812 AC: 4204 AN: 5178

South Asian (SAS) AF: 0.772 AC: 3725 AN: 4824

European-Finnish (FIN) AF: 0.769 AC: 8147 AN: 10588

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49030 AN: 67944

Other (OTH) AF: 0.759 AC: 1604 AN: 2112

Alfa AF: 0.736 Hom.: 169322

Bravo AF: 0.772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		-0.24
PromoterAI		0.013	Neutral
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: rs526934; hg19: chr11-59633493;