rs173665

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4	c.*433C>T		downstream_gene_variant		ENST00000301458.10	NP_057663.1
CD320	NM_001165895.2	c.*433C>T		downstream_gene_variant			NP_001159367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10	c.*433C>T		downstream_gene_variant		1	NM_016579.4	ENSP00000301458.4
CD320	ENST00000596002.5	n.*1570C>T		downstream_gene_variant		1		ENSP00000471773.1
CD320	ENST00000537716.6	c.*433C>T		downstream_gene_variant		2		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

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0595

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.0858

Gnomad4 NFE exome AF: 0.0935

Gnomad4 OTH exome AF: 0.109

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

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.0941

Gnomad4 OTH AF: 0.112

Alfa AF: 0.110 Hom.: 93

Bravo AF: 0.111

Asia WGS AF: 0.177 AC: 615 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	0.23
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

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