rs519221

Variant names:

• chr11-59857063-A-T
• rs519221
• NM_001062.4:c.748-1005T>A

Variant summary

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

The NM_001062.4(TCN1):​c.748-1005T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,026 control chromosomes in the GnomAD database, including 5,543 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 0.26 (5543 hom., cov: 32)
• Consequence: TCN1 NM_001062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCN1	NM_001062.4	c.748-1005T>A		intron_variant	Intron 5 of 8	ENST00000257264.4	NP_001053.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCN1	ENST00000257264.4	c.748-1005T>A		intron_variant	Intron 5 of 8	1	NM_001062.4	ENSP00000257264.3
TCN1	ENST00000532419.5	n.576-2228T>A		intron_variant	Intron 4 of 4	5
TCN1	ENST00000534531.1	n.569-1005T>A		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40248 AN: 151908 Hom.: 5545 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.265 AC: 40260 AN: 152026 Hom.: 5543 Cov.: 32 AF XY: 0.265 AC XY: 19661 AN XY: 74286

African (AFR) AF: 0.310 AC: 12857 AN: 41446

American (AMR) AF: 0.166 AC: 2545 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.170 AC: 880 AN: 5178

South Asian (SAS) AF: 0.274 AC: 1322 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2917 AN: 10546

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18195 AN: 67954

Other (OTH) AF: 0.212 AC: 448 AN: 2116

Alfa AF: 0.265 Hom.: 643

Bravo AF: 0.256

Asia WGS AF: 0.210 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.74
PhyloP100		1.1
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: rs519221; hg19: chr11-59624536;