chr22-30622574-T-G

Position:

• chr22-30622574-T-G

Variant summary

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

The ENST00000215838.8(TCN2):​c.1107-394T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,064 control chromosomes in the GnomAD database, including 10,086 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 0.35 (10086 hom., cov: 32)
• Consequence: TCN2 ENST00000215838.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCN2	NM_000355.4	c.1107-394T>G		intron_variant		ENST00000215838.8	NP_000346.2
TCN2	NM_001184726.2	c.1026-394T>G		intron_variant			NP_001171655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCN2	ENST00000215838.8	c.1107-394T>G		intron_variant		1	NM_000355.4	ENSP00000215838	P2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53971 AN: 151944 Hom.: 10083 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.355 AC: 53979 AN: 152064 Hom.: 10086 Cov.: 32 AF XY: 0.353 AC XY: 26227 AN XY: 74306

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.366

Alfa AF: 0.264 Hom.: 659

Bravo AF: 0.344

Asia WGS AF: 0.264 AC: 920 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	0.43
DANN	Benign	0.62

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: rs7286680; hg19: chr22-31018561;