chr19-8302475-G-C

Position:

• chr19-8302475-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016579.4(CD320):​c.837C>G​(p.Thr279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,614,016 control chromosomes in the GnomAD database, including 4,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2032 hom., cov: 32)
  • Exomes 𝑓: 0.044 (2798 hom.)
• Consequence: CD320 NM_016579.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.137

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-8302475-G-C is Benign according to our data. Variant chr19-8302475-G-C is described in ClinVar as [Benign]. Clinvar id is 136686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.137 with no splicing effect.
• 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/exons	MANE	Protein	UniProt
CD320	NM_016579.4	c.837C>G	p.Thr279=	synonymous_variant	5/5	ENST00000301458.10	NP_057663.1
CD320	NM_001165895.2	c.711C>G	p.Thr237=	synonymous_variant	4/4		NP_001159367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10	c.837C>G	p.Thr279=	synonymous_variant	5/5	1	NM_016579.4	ENSP00000301458	P1
CD320	ENST00000596002.5	c.*1125C>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000471773
CD320	ENST00000537716.6	c.711C>G	p.Thr237=	synonymous_variant	4/4	2		ENSP00000437697
CD320	ENST00000599573.1	c.*437C>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2		ENSP00000471551

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17380 AN: 152098 Hom.: 2024 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0590 AC: 14826 AN: 251384 Hom.: 1005 AF XY: 0.0534 AC XY: 7261 AN XY: 135886

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.0455

Gnomad ASJ exome AF: 0.0634

Gnomad EAS exome AF: 0.0883

Gnomad SAS exome AF: 0.0363

Gnomad FIN exome AF: 0.0272

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0437 AC: 63862 AN: 1461800 Hom.: 2798 Cov.: 33 AF XY: 0.0425 AC XY: 30870 AN XY: 727202

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0611

Gnomad4 EAS exome AF: 0.0728

Gnomad4 SAS exome AF: 0.0346

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.0345

Gnomad4 OTH exome AF: 0.0594

GnomAD4 genome AF: 0.114 AC: 17410 AN: 152216 Hom.: 2032 Cov.: 32 AF XY: 0.113 AC XY: 8427 AN XY: 74432

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0886

Gnomad4 SAS AF: 0.0391

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0348 Hom.: 65

Bravo AF: 0.127

Asia WGS AF: 0.0810 AC: 283 AN: 3478

EpiCase AF: 0.0425

EpiControl AF: 0.0385

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2013

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

not provided Benign:1

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	-0.86
CADD	Benign	0.65
DANN	Benign	0.39
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

Other links and lift over

dbSNP: rs2227289; hg19: chr19-8367359;