19-8302274-C-T

Variant summary

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

The NM_016579.4(CD320):c.*189G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 756,224 control chromosomes in the GnomAD database, including 3,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2028 hom., cov: 33)
  • Exomes 𝑓: 0.046 (1274 hom.)
• Consequence: CD320 NM_016579.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0440

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-8302274-C-T is Benign according to our data. Variant chr19-8302274-C-T is described in ClinVar as [Benign]. Clinvar id is 1239139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD320	NM_016579.4	c.*189G>A		3_prime_UTR_variant	5/5	ENST00000301458.10
CD320	NM_001165895.2	c.*189G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD320	ENST00000301458.10	c.*189G>A		3_prime_UTR_variant	5/5	1	NM_016579.4	P1
CD320	ENST00000596002.5	c.*1326G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	1
CD320	ENST00000537716.6	c.*189G>A		3_prime_UTR_variant	4/4	2
CD320	ENST00000599573.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17370 AN: 152098 Hom.: 2020 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0549 AC: 8506 AN: 154816 Hom.: 487 AF XY: 0.0513 AC XY: 4350 AN XY: 84850

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.0456

Gnomad ASJ exome AF: 0.0634

Gnomad EAS exome AF: 0.0855

Gnomad SAS exome AF: 0.0343

Gnomad FIN exome AF: 0.0274

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0464

GnomAD4 exome AF: 0.0458 AC: 27681 AN: 604008 Hom.: 1274 Cov.: 7 AF XY: 0.0433 AC XY: 14097 AN XY: 325296

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0481

Gnomad4 ASJ exome AF: 0.0610

Gnomad4 EAS exome AF: 0.0679

Gnomad4 SAS exome AF: 0.0342

Gnomad4 FIN exome AF: 0.0281

Gnomad4 NFE exome AF: 0.0334

Gnomad4 OTH exome AF: 0.0612

GnomAD4 genome AF: 0.114 AC: 17401 AN: 152216 Hom.: 2028 Cov.: 33 AF XY: 0.113 AC XY: 8430 AN XY: 74428

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0521 Hom.: 311

Bravo AF: 0.127

Asia WGS AF: 0.0810 AC: 283 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 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.7
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs9426; hg19: chr19-8367158; COSMIC: COSV56847980; COSMIC: COSV56847980;