rs4820886

chr22-30620552-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000355.4(TCN2):c.1107-2416T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,246 control chromosomes in the GnomAD database, including 1,416 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 0.13 (1416 hom., cov: 33)
• Consequence: TCN2 NM_000355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

Genes affected

TCN2 (HGNC:11653): (transcobalamin 2) 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 plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCN2	NM_000355.4	c.1107-2416T>G		intron_variant		ENST00000215838.8
TCN2	NM_001184726.2	c.1026-2416T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCN2	ENST00000215838.8	c.1107-2416T>G		intron_variant		1	NM_000355.4	P2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19777 AN: 152128 Hom.: 1411 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0859

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.130 AC: 19805 AN: 152246 Hom.: 1416 Cov.: 33 AF XY: 0.131 AC XY: 9759 AN XY: 74456

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.124

Alfa AF: 0.113 Hom.: 456

Bravo AF: 0.130

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.6
Dann	Benign	0.40

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: rs4820886; hg19: chr22-31016539;