Genetic Variant NM_016579.4:c.707-15A>T (chr19-8302620-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_016579.4(CD320):c.707-15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,611,924 control chromosomes in the GnomAD database, including 7,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 661 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7069 hom. )

Consequence

CD320
NM_016579.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.07

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=-0.83).

BP6

Variant 19-8302620-T-A is Benign according to our data. Variant chr19-8302620-T-A is described in ClinVar as [Benign]. Clinvar id is 136685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4 link	c.707-15A>T		intron_variant	Intron 4 of 4	ENST00000301458.10	NP_057663.1	Q9NPF0-1
CD320	NM_001165895.2 link	c.581-15A>T		intron_variant	Intron 3 of 3		NP_001159367.1	Q9NPF0-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD320	ENST00000301458.10 link	c.707-15A>T	intron_variant	Intron 4 of 4	1	NM_016579.4	ENSP00000301458.4	Q9NPF0-1
CD320	ENST00000596002.5 link	n.*995-15A>T	intron_variant	Intron 4 of 4	1		ENSP00000471773.1	M0R1C4
CD320	ENST00000537716.6 link	c.581-15A>T	intron_variant	Intron 3 of 3	2		ENSP00000437697.1	Q9NPF0-2
CD320	ENST00000599573.1 link	n.*307-15A>T	intron_variant	Intron 4 of 4	2		ENSP00000471551.1	M0R100

Frequencies

GnomAD3 genomes

AF:

0.0883

AC:

13411

AN:

151938

Hom.:

662

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0753

Gnomad AMI

AF:

0.0826

Gnomad AMR

AF:

0.0664

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0825

Gnomad FIN

AF:

0.0858

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0938

Gnomad OTH

AF:

0.0948

GnomAD3 exomes

AF:

0.0886

AC:

22092

AN:

249236

Hom.:

1152

AF XY:

0.0902

AC XY:

12160

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.0750

Gnomad AMR exome

AF:

0.0414

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.0780

Gnomad FIN exome

AF:

0.0895

Gnomad NFE exome

AF:

0.0936

Gnomad OTH exome

AF:

0.0922

GnomAD4 exome

AF:

0.0962

AC:

140429

AN:

1459868

Hom.:

7069

Cov.:

AF XY:

0.0962

AC XY:

69850

AN XY:

725918

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.0443

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.0774

Gnomad4 FIN exome

AF:

0.0901

Gnomad4 NFE exome

AF:

0.0972

Gnomad4 OTH exome

AF:

0.0997

GnomAD4 genome

AF:

0.0883

AC:

13419

AN:

152056

Hom.:

661

Cov.:

AF XY:

0.0872

AC XY:

6481

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0754

Gnomad4 AMR

AF:

0.0662

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.0830

Gnomad4 FIN

AF:

0.0858

Gnomad4 NFE

AF:

0.0938

Gnomad4 OTH

AF:

0.0948

Alfa

AF:

0.0682

Hom.:

119

Bravo

AF:

0.0867

Asia WGS

AF:

0.0960

AC:

332

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 09, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Methylmalonic acidemia due to transcobalamin receptor defect

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.15

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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