dbSNP rs17160390: CD320:c.143-769T>C (chr19-8305925-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

2 publications found

Variant links:

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

CD320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4 link	c.143-769T>C		intron_variant	Intron 1 of 4	ENST00000301458.10	NP_057663.1	Q9NPF0-1
CD320	NM_001165895.2 link	c.143-1837T>C		intron_variant	Intron 1 of 3		NP_001159367.1	Q9NPF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10 link	c.143-769T>C		intron_variant	Intron 1 of 4	1	NM_016579.4	ENSP00000301458.4		Q9NPF0-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17334

AN:

151900

Hom.:

2024

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.0385

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0345

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.114

AC:

17365

AN:

152018

Hom.:

2032

Cov.:

AF XY:

0.113

AC XY:

8412

AN XY:

74330

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.0348

AC:

2364

AN:

68004

Other (OTH)

AF:

0.102

AC:

214

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

683

1366

2050

2733

3416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.5

(source)

DANN

Benign

0.61

PhyloP100

-0.066

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over