rs2000613

Positions:

• chr11-59863363-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001062.4(TCN1):​c.259+544C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 152,102 control chromosomes in the GnomAD database, including 102 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 0.029 (102 hom., cov: 32)
• Consequence: TCN1 NM_001062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.029 (4411/152102) while in subpopulation NFE AF= 0.0434 (2947/67970). AF 95% confidence interval is 0.0421. There are 102 homozygotes in gnomad4. There are 2230 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 102 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN1	NM_001062.4	c.259+544C>A		intron_variant		ENST00000257264.4	NP_001053.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN1	ENST00000257264.4	c.259+544C>A		intron_variant		1	NM_001062.4	ENSP00000257264.3
TCN1	ENST00000532419.5	n.278+544C>A		intron_variant		5
TCN1	ENST00000534531.1	n.81-641C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4410 AN: 151984 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.00785

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0290 AC: 4411 AN: 152102 Hom.: 102 Cov.: 32 AF XY: 0.0300 AC XY: 2230 AN XY: 74354

Gnomad4 AFR AF: 0.00783

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.0434

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0344 Hom.: 11

Bravo AF: 0.0238

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.67

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: rs2000613; hg19: chr11-59630836;