Variant rs2227288 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016579.4(CD320):c.707-36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,608,938 control chromosomes in the GnomAD database, including 12,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1689 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10592 hom. )

Consequence

CD320
NM_016579.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.555

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-8302641-G-C is Benign according to our data. Variant chr19-8302641-G-C is described in ClinVar as [Benign]. Clinvar id is 1248253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD320	NM_016579.4 linkuse as main transcript	c.707-36C>G		intron_variant		ENST00000301458.10	NP_057663.1
CD320	NM_001165895.2 linkuse as main transcript	c.581-36C>G		intron_variant			NP_001159367.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10 linkuse as main transcript	c.707-36C>G	intron_variant	1	NM_016579.4	ENSP00000301458	P1	Q9NPF0-1
CD320	ENST00000596002.5 linkuse as main transcript	c.*995-36C>G	intron_variant, NMD_transcript_variant	1		ENSP00000471773
CD320	ENST00000537716.6 linkuse as main transcript	c.581-36C>G	intron_variant	2		ENSP00000437697		Q9NPF0-2
CD320	ENST00000599573.1 linkuse as main transcript	c.*307-36C>G	intron_variant, NMD_transcript_variant	2		ENSP00000471551

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21413

AN:

151976

Hom.:

1689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0679

Gnomad SAS

AF:

0.0921

Gnomad FIN

AF:

0.0602

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.146

GnomAD3 exomes

AF:

0.121

AC:

29892

AN:

247986

Hom.:

1924

AF XY:

0.121

AC XY:

16254

AN XY:

134158

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0721

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0611

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.117

AC:

170128

AN:

1456844

Hom.:

10592

Cov.:

AF XY:

0.117

AC XY:

84762

AN XY:

723826

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.0693

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0645

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.141

AC:

21427

AN:

152094

Hom.:

1689

Cov.:

AF XY:

0.139

AC XY:

10309

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0678

Gnomad4 SAS

AF:

0.0922

Gnomad4 FIN

AF:

0.0602

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.134

Hom.:

266

Bravo

AF:

0.152

Asia WGS

AF:

0.0870

AC:

301

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.20

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over