chr19-8302334-G-A

Variant names:

• chr19-8302334-G-A
• rs2232788
• NM_016579.4:c.*129C>T

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.*129C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,163,048 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (54 hom.)
• Consequence: CD320 NM_016579.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18
• Publications: 5 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=-0.92).
• BP6: Variant 19-8302334-G-A is Benign according to our data. Variant chr19-8302334-G-A is described in ClinVar as Benign. ClinVar VariationId is 1181546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 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.*129C>T		3_prime_UTR	Exon 5 of 5	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.*129C>T		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.*129C>T		3_prime_UTR	Exon 5 of 5	ENSP00000301458.4	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*1266C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000471773.1	M0R1C4
	CD320	ENST00000596002.5	TSL:1	n.*1266C>T		3_prime_UTR	Exon 5 of 5	ENSP00000471773.1	M0R1C4

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2393 AN: 152134 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00369 AC: 873 AN: 236618 AF XY: 0.00303

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.00175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000822

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00167 AC: 1687 AN: 1010796 Hom.: 54 Cov.: 13 AF XY: 0.00143 AC XY: 749 AN XY: 522308

African (AFR) AF: 0.0579 AC: 1420 AN: 24536

American (AMR) AF: 0.00196 AC: 86 AN: 43928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23276

East Asian (EAS) AF: 0.0000265 AC: 1 AN: 37702

South Asian (SAS) AF: 0.0000652 AC: 5 AN: 76698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41362

Middle Eastern (MID) AF: 0.00162 AC: 8 AN: 4932

European-Non Finnish (NFE) AF: 0.0000393 AC: 28 AN: 712496

Other (OTH) AF: 0.00303 AC: 139 AN: 45866

GnomAD4 genome AF: 0.0159 AC: 2417 AN: 152252 Hom.: 62 Cov.: 33 AF XY: 0.0159 AC XY: 1181 AN XY: 74452

African (AFR) AF: 0.0562 AC: 2333 AN: 41528

American (AMR) AF: 0.00392 AC: 60 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68010

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00447 Hom.: 23

Bravo AF: 0.0170

Asia WGS AF: 0.00404 AC: 14 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	-0.92
CADD	Benign	0.34
DANN	Benign	0.53
PhyloP100		-1.2
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: rs2232788; hg19: chr19-8367218; COSMIC: COSV56848600; COSMIC: COSV56848600;