rs2232785

Variant names:

• chr19-8303737-C-T
• rs2232785
• NM_016579.4:c.502+118G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016579.4(CD320):​c.502+118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 725,596 control chromosomes in the GnomAD database, including 3,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2037 hom., cov: 33)
  • Exomes 𝑓: 0.046 (1220 hom.)
• Consequence: CD320 NM_016579.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-8303737-C-T is Benign according to our data. Variant chr19-8303737-C-T is described in ClinVar as Benign. ClinVar VariationId is 1292290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 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.502+118G>A		intron	N/A	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.376+118G>A		intron	N/A	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.502+118G>A		intron	N/A	ENSP00000301458.4	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*790+118G>A		intron	N/A	ENSP00000471773.1	M0R1C4
	CD320	ENST00000963189.1		c.814+118G>A		intron	N/A	ENSP00000633248.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17404 AN: 152142 Hom.: 2029 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0460 AC: 26397 AN: 573336 Hom.: 1220 AF XY: 0.0436 AC XY: 13219 AN XY: 303480

African (AFR) AF: 0.296 AC: 4769 AN: 16096

American (AMR) AF: 0.0489 AC: 1633 AN: 33376

Ashkenazi Jewish (ASJ) AF: 0.0607 AC: 1152 AN: 18982

East Asian (EAS) AF: 0.0691 AC: 2187 AN: 31660

South Asian (SAS) AF: 0.0341 AC: 2067 AN: 60586

European-Finnish (FIN) AF: 0.0286 AC: 950 AN: 33230

Middle Eastern (MID) AF: 0.0640 AC: 160 AN: 2500

European-Non Finnish (NFE) AF: 0.0334 AC: 11575 AN: 346124

Other (OTH) AF: 0.0619 AC: 1904 AN: 30782

GnomAD4 genome AF: 0.115 AC: 17435 AN: 152260 Hom.: 2037 Cov.: 33 AF XY: 0.113 AC XY: 8441 AN XY: 74454

African (AFR) AF: 0.303 AC: 12597 AN: 41520

American (AMR) AF: 0.0686 AC: 1050 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.0882 AC: 458 AN: 5190

South Asian (SAS) AF: 0.0395 AC: 191 AN: 4832

European-Finnish (FIN) AF: 0.0299 AC: 317 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0348 AC: 2365 AN: 68020

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0907 Hom.: 173

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 286 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2232785; hg19: chr19-8368621; COSMIC: COSV56847985; COSMIC: COSV56847985;