19-8302380-G-C

Position:

• chr19-8302380-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016579.4(CD320):​c.*83C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,551,686 control chromosomes in the GnomAD database, including 1,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (175 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1255 hom.)
• Consequence: CD320 NM_016579.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.280

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-8302380-G-C is Benign according to our data. Variant chr19-8302380-G-C is described in ClinVar as [Benign]. Clinvar id is 1249046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD320	NM_016579.4	c.*83C>G		3_prime_UTR_variant	5/5	ENST00000301458.10	NP_057663.1
CD320	NM_001165895.2	c.*83C>G		3_prime_UTR_variant	4/4		NP_001159367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10	c.*83C>G		3_prime_UTR_variant	5/5	1	NM_016579.4	ENSP00000301458	P1
CD320	ENST00000596002.5	c.*1220C>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000471773
CD320	ENST00000537716.6	c.*83C>G		3_prime_UTR_variant	4/4	2		ENSP00000437697
CD320	ENST00000599573.1	c.*532C>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	2		ENSP00000471551

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3395 AN: 152140 Hom.: 174 Cov.: 33

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0234 AC: 5795 AN: 248054 Hom.: 421 AF XY: 0.0291 AC XY: 3910 AN XY: 134504

Gnomad AFR exome AF: 0.0591

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00131

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000478

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.0115 AC: 16053 AN: 1399428 Hom.: 1255 Cov.: 25 AF XY: 0.0157 AC XY: 10957 AN XY: 699528

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000659

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000193

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0223 AC: 3401 AN: 152258 Hom.: 175 Cov.: 33 AF XY: 0.0243 AC XY: 1808 AN XY: 74446

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00195 Hom.: 2

Bravo AF: 0.0206

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 25, 2021	- -
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	-0.82
CADD	Benign	1.2
DANN	Benign	0.54

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: rs199841056; hg19: chr19-8367264;