rs9426

Variant names:

• chr19-8302274-C-T
• rs9426
• NM_016579.4:c.*189G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_016579.4(CD320):​c.*189G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 756,224 control chromosomes in the GnomAD database, including 3,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2028 hom., cov: 33)
  • Exomes 𝑓: 0.046 (1274 hom.)
• Consequence: CD320 NM_016579.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0440
• Publications: 19 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: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.047).
• BP6: Variant 19-8302274-C-T is Benign according to our data. Variant chr19-8302274-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 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.*189G>A		3_prime_UTR	Exon 5 of 5	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.*189G>A		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.*189G>A		3_prime_UTR	Exon 5 of 5	ENSP00000301458.4	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*1326G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000471773.1	M0R1C4
	CD320	ENST00000596002.5	TSL:1	n.*1326G>A		3_prime_UTR	Exon 5 of 5	ENSP00000471773.1	M0R1C4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17370 AN: 152098 Hom.: 2020 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0549 AC: 8506 AN: 154816 AF XY: 0.0513

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.0456

Gnomad ASJ exome AF: 0.0634

Gnomad EAS exome AF: 0.0855

Gnomad FIN exome AF: 0.0274

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0464

GnomAD4 exome AF: 0.0458 AC: 27681 AN: 604008 Hom.: 1274 Cov.: 7 AF XY: 0.0433 AC XY: 14097 AN XY: 325296

African (AFR) AF: 0.296 AC: 4952 AN: 16730

American (AMR) AF: 0.0481 AC: 1694 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.0610 AC: 1236 AN: 20278

East Asian (EAS) AF: 0.0679 AC: 2211 AN: 32542

South Asian (SAS) AF: 0.0342 AC: 2201 AN: 64388

European-Finnish (FIN) AF: 0.0281 AC: 953 AN: 33878

Middle Eastern (MID) AF: 0.0676 AC: 281 AN: 4156

European-Non Finnish (NFE) AF: 0.0334 AC: 12172 AN: 364456

Other (OTH) AF: 0.0612 AC: 1981 AN: 32378

GnomAD4 genome AF: 0.114 AC: 17401 AN: 152216 Hom.: 2028 Cov.: 33 AF XY: 0.113 AC XY: 8430 AN XY: 74428

African (AFR) AF: 0.303 AC: 12569 AN: 41492

American (AMR) AF: 0.0686 AC: 1049 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.0882 AC: 456 AN: 5172

South Asian (SAS) AF: 0.0395 AC: 191 AN: 4834

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0348 AC: 2365 AN: 68016

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0573 Hom.: 431

Bravo AF: 0.127

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		-0.044
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs9426; hg19: chr19-8367158; COSMIC: COSV56847980; COSMIC: COSV56847980;