rs17160390

chr19-8305925-A-G

Variant summary

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

The NM_016579.4(CD320):c.143-769T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,098 control chromosomes in the GnomAD database, including 2,032 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 (2032 hom., cov: 31)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: CD320 NM_016579.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD320	NM_016579.4	c.143-769T>C		intron_variant		ENST00000301458.10
CD320	NM_001165895.2	c.143-1837T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD320	ENST00000301458.10	c.143-769T>C		intron_variant		1	NM_016579.4	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17334 AN: 151900 Hom.: 2024 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0375 AC: 3 AN: 80 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 2 AN XY: 52

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0345

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.114 AC: 17365 AN: 152018 Hom.: 2032 Cov.: 31 AF XY: 0.113 AC XY: 8412 AN XY: 74330

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0827 Hom.: 137

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.5
Dann	Benign	0.61

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: rs17160390; hg19: chr19-8370809;