19-8302380-G-C

Variant names:

• chr19-8302380-G-C
• rs199841056
• NM_016579.4:c.*83C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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: Laboratory for Molecular Medicine, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.*83C>G		3_prime_UTR	Exon 5 of 5	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.*83C>G		3_prime_UTR	Exon 4 of 4	NP_001159367.1	Q9NPF0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	ENST00000301458.10	TSL:1 MANE Select	c.*83C>G		3_prime_UTR	Exon 5 of 5	ENSP00000301458.4	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*1220C>G		non_coding_transcript_exon	Exon 5 of 5	ENSP00000471773.1	M0R1C4
	CD320	ENST00000596002.5	TSL:1	n.*1220C>G		3_prime_UTR	Exon 5 of 5	ENSP00000471773.1	M0R1C4

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

GnomAD2 exomes AF: 0.0234 AC: 5795 AN: 248054 AF XY: 0.0291

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 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

African (AFR) AF: 0.0612 AC: 1966 AN: 32128

American (AMR) AF: 0.00287 AC: 128 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.000659 AC: 26 AN: 39434

South Asian (SAS) AF: 0.152 AC: 12890 AN: 84806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50048

Middle Eastern (MID) AF: 0.0148 AC: 84 AN: 5664

European-Non Finnish (NFE) AF: 0.000193 AC: 204 AN: 1058574

Other (OTH) AF: 0.0129 AC: 755 AN: 58394

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

African (AFR) AF: 0.0581 AC: 2414 AN: 41542

American (AMR) AF: 0.00556 AC: 85 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.174 AC: 836 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68016

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00195 Hom.: 2

Bravo AF: 0.0206

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs199841056; hg19: chr19-8367264;