rs17160390

Variant names:

• chr19-8305925-A-G
• rs17160390
• NM_016579.4:c.143-769T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.143-769T>C		intron	N/A	NP_057663.1
	CD320	NM_001165895.2		c.143-1837T>C		intron	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.143-769T>C		intron	N/A	ENSP00000301458.4
	CD320	ENST00000596002.5	TSL:1	n.143-120T>C		intron	N/A	ENSP00000471773.1
	CD320	ENST00000537716.6	TSL:2	c.143-1837T>C		intron	N/A	ENSP00000437697.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0345 AC: 2 AN: 58

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.303 AC: 12545 AN: 41382

American (AMR) AF: 0.0683 AC: 1043 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3466

East Asian (EAS) AF: 0.0876 AC: 454 AN: 5180

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4818

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10600

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0348 AC: 2364 AN: 68004

Other (OTH) AF: 0.102 AC: 214 AN: 2106

Alfa AF: 0.0908 Hom.: 173

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17160390; hg19: chr19-8370809;