rs740234

chr22-30612758-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000355.4(TCN2):c.258-115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,332,756 control chromosomes in the GnomAD database, including 23,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2081 hom., cov: 32)
  • Exomes 𝑓: 0.18 (21326 hom.)
• Consequence: TCN2 NM_000355.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.858

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-30612758-A-G is Benign according to our data. Variant chr22-30612758-A-G is described in ClinVar as [Benign]. Clinvar id is 1269240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCN2	NM_000355.4	c.258-115A>G		intron_variant		ENST00000215838.8
TCN2	NM_001184726.2	c.258-115A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCN2	ENST00000215838.8	c.258-115A>G		intron_variant		1	NM_000355.4	P2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24128 AN: 152028 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.181 AC: 214206 AN: 1180610 Hom.: 21326 AF XY: 0.179 AC XY: 105511 AN XY: 590104

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.000337

Gnomad4 SAS exome AF: 0.0919

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.159 AC: 24137 AN: 152146 Hom.: 2081 Cov.: 32 AF XY: 0.157 AC XY: 11642 AN XY: 74368

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.168

Alfa AF: 0.192 Hom.: 5713

Bravo AF: 0.155

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.8
Dann	Benign	0.51

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: rs740234; hg19: chr22-31008745;