rs2000613

Variant names:

• chr11-59863363-G-T
• rs2000613
• NM_001062.4:c.259+544C>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.91).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 102 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCN1	NM_001062.4	c.259+544C>A		intron_variant	Intron 2 of 8	ENST00000257264.4	NP_001053.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCN1	ENST00000257264.4	c.259+544C>A		intron_variant	Intron 2 of 8	1	NM_001062.4	ENSP00000257264.3
TCN1	ENST00000532419.5	n.278+544C>A		intron_variant	Intron 2 of 4	5
TCN1	ENST00000534531.1	n.81-641C>A		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.00783 AC: 325 AN: 41500

American (AMR) AF: 0.0166 AC: 253 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4824

European-Finnish (FIN) AF: 0.0743 AC: 786 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0434 AC: 2947 AN: 67970

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0366 Hom.: 184

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
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism

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: rs2000613; hg19: chr11-59630836;