Genetic Variant NM_016579.4: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: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

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.

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

Sel.	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	Q9NPF0-1
	CD320	NM_001165895.2		c.143-1837T>C		intron	N/A	NP_001159367.1	Q9NPF0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD320	ENST00000301458.10	TSL:1 MANE Select	c.143-769T>C	intron	N/A	ENSP00000301458.4	Q9NPF0-1
CD320	ENST00000596002.5	TSL:1	n.143-120T>C	intron	N/A	ENSP00000471773.1	M0R1C4
CD320	ENST00000963189.1		c.454+747T>C	intron	N/A	ENSP00000633248.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over