dbSNP rs173665: CD320:c.*433C>T (chr19-8302030-G-A) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.544

Publications

5 publications found

Variant links:

COSMIC-nc: COSV56848527

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=-0.91).

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 link	c.*433C>T		downstream_gene_variant		ENST00000301458.10	NP_057663.1	Q9NPF0-1
CD320	NM_001165895.2 link	c.*433C>T		downstream_gene_variant			NP_001159367.1	Q9NPF0-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CD320	ENST00000301458.10 link	c.*433C>T	downstream_gene_variant	1	NM_016579.4	ENSP00000301458.4	Q9NPF0-1
CD320	ENST00000596002.5 link	n.*1570C>T	downstream_gene_variant	1		ENSP00000471773.1	M0R1C4
CD320	ENST00000537716.6 link	c.*433C>T	downstream_gene_variant	2		ENSP00000437697.1	Q9NPF0-2

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17305

AN:

152130

Hom.:

1168

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.156

AC:

863

AN:

5520

American (AMR)

AF:

0.0595

AC:

705

AN:

11850

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

690

AN:

4762

East Asian (EAS)

AF:

0.145

AC:

1231

AN:

8498

South Asian (SAS)

AF:

0.226

AC:

9746

AN:

43190

European-Finnish (FIN)

AF:

0.0858

AC:

813

AN:

9472

Middle Eastern (MID)

AF:

0.122

AC:

AN:

698

European-Non Finnish (NFE)

AF:

0.0935

AC:

10726

AN:

114692

Other (OTH)

AF:

0.109

AC:

1096

AN:

10028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1198

2397

3595

4794

5992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.114

AC:

17320

AN:

152248

Hom.:

1169

Cov.:

AF XY:

0.114

AC XY:

8510

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.145

AC:

6013

AN:

41538

American (AMR)

AF:

0.0729

AC:

1115

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

572

AN:

3472

East Asian (EAS)

AF:

0.142

AC:

732

AN:

5168

South Asian (SAS)

AF:

0.255

AC:

1229

AN:

4826

European-Finnish (FIN)

AF:

0.0858

AC:

911

AN:

10612

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0941

AC:

6401

AN:

68020

Other (OTH)

AF:

0.112

AC:

237

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

782

1564

2347

3129

3911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<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:

0.102

Hom.:

2059

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

(source)

DANN

Benign

0.28

PhyloP100

-0.54

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over