chr19-8302030-G-A

Variant names:

• chr19-8302030-G-A
• rs173665
• NM_016579.4:c.*433C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016579.4(CD320):​c.*433C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 360,958 control chromosomes in the GnomAD database, including 3,249 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 0.11 (1169 hom., cov: 31)
  • Exomes 𝑓: 0.12 (2080 hom.)
• Consequence: CD320 NM_016579.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 5 publications found

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]

CD320 Gene-Disease associations (from GenCC):

• methylmalonic acidemia due to transcobalamin receptor defect

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.*433C>T		downstream_gene	N/A	NP_057663.1
	CD320	NM_001165895.2		c.*433C>T		downstream_gene	N/A	NP_001159367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	ENST00000301458.10	TSL:1 MANE Select	c.*433C>T		downstream_gene	N/A	ENSP00000301458.4
	CD320	ENST00000596002.5	TSL:1	n.*1570C>T		downstream_gene	N/A	ENSP00000471773.1
	CD320	ENST00000537716.6	TSL:2	c.*433C>T		downstream_gene	N/A	ENSP00000437697.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17305 AN: 152130 Hom.: 1168 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.124 AC: 25955 AN: 208710 Hom.: 2080 AF XY: 0.137 AC XY: 15679 AN XY: 114352

African (AFR) AF: 0.156 AC: 863 AN: 5520

American (AMR) AF: 0.0595 AC: 705 AN: 11850

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 690 AN: 4762

East Asian (EAS) AF: 0.145 AC: 1231 AN: 8498

South Asian (SAS) AF: 0.226 AC: 9746 AN: 43190

European-Finnish (FIN) AF: 0.0858 AC: 813 AN: 9472

Middle Eastern (MID) AF: 0.122 AC: 85 AN: 698

European-Non Finnish (NFE) AF: 0.0935 AC: 10726 AN: 114692

Other (OTH) AF: 0.109 AC: 1096 AN: 10028

GnomAD4 genome AF: 0.114 AC: 17320 AN: 152248 Hom.: 1169 Cov.: 31 AF XY: 0.114 AC XY: 8510 AN XY: 74440

African (AFR) AF: 0.145 AC: 6013 AN: 41538

American (AMR) AF: 0.0729 AC: 1115 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3472

East Asian (EAS) AF: 0.142 AC: 732 AN: 5168

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4826

European-Finnish (FIN) AF: 0.0858 AC: 911 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6401 AN: 68020

Other (OTH) AF: 0.112 AC: 237 AN: 2116

Alfa AF: 0.102 Hom.: 2059

Bravo AF: 0.111

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.28
PhyloP100		-0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs173665; hg19: chr19-8366914; COSMIC: COSV56848527;