rs519221

chr11-59857063-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TCN1	NM_001062.4	c.748-1005T>A		intron_variant		ENST00000257264.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCN1	ENST00000257264.4	c.748-1005T>A		intron_variant		1	NM_001062.4	P1
TCN1	ENST00000532419.5	n.576-2228T>A		intron_variant, non_coding_transcript_variant		5
TCN1	ENST00000534531.1	n.569-1005T>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.212

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

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: rs519221; hg19: chr11-59624536;