22-30620927-G-A

Position:

• chr22-30620927-G-A

Variant summary

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

The NM_000355.4(TCN2):​c.1107-2041G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,186 control chromosomes in the GnomAD database, including 902 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 0.10 (902 hom., cov: 33)
• Consequence: TCN2 NM_000355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN2	NM_000355.4	c.1107-2041G>A		intron_variant		ENST00000215838.8	NP_000346.2
TCN2	NM_001184726.2	c.1026-2041G>A		intron_variant			NP_001171655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8	c.1107-2041G>A		intron_variant		1	NM_000355.4	ENSP00000215838	P2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15685 AN: 152068 Hom.: 897 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.103 AC: 15706 AN: 152186 Hom.: 902 Cov.: 33 AF XY: 0.106 AC XY: 7853 AN XY: 74404

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0819

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0746

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0956

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.0922 Hom.: 350

Bravo AF: 0.101

Asia WGS AF: 0.0420 AC: 147 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	0.53
DANN	Benign	0.52

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: rs4820887; hg19: chr22-31016914;