rs2232783

Variant names:

• chr19-8303910-C-A
• rs2232783
• NM_016579.4:c.447G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8303910-C-A
• chr19-8303910-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_016579.4(CD320):​c.447G>T​(p.Thr149Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 1,605,668 control chromosomes in the GnomAD database, including 4,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2043 hom., cov: 34)
  • Exomes 𝑓: 0.044 (2762 hom.)
• Consequence: CD320 NM_016579.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.60
• Publications: 13 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 19-8303910-C-A is Benign according to our data. Variant chr19-8303910-C-A is described in ClinVar as Benign. ClinVar VariationId is 136680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.6 with no splicing effect.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	NM_016579.4	MANE Select	c.447G>T	p.Thr149Thr	synonymous	Exon 3 of 5	NP_057663.1
	CD320	NM_001165895.2		c.321G>T	p.Thr107Thr	synonymous	Exon 2 of 4	NP_001159367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD320	ENST00000301458.10	TSL:1 MANE Select	c.447G>T	p.Thr149Thr	synonymous	Exon 3 of 5	ENSP00000301458.4
	CD320	ENST00000596002.5	TSL:1	n.*735G>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000471773.1
	CD320	ENST00000596002.5	TSL:1	n.*735G>T		3_prime_UTR	Exon 3 of 5	ENSP00000471773.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17412 AN: 152190 Hom.: 2035 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0571 AC: 13345 AN: 233538 AF XY: 0.0517

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.0447

Gnomad ASJ exome AF: 0.0624

Gnomad EAS exome AF: 0.0873

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0342

Gnomad OTH exome AF: 0.0470

GnomAD4 exome AF: 0.0435 AC: 63291 AN: 1453360 Hom.: 2762 Cov.: 32 AF XY: 0.0423 AC XY: 30563 AN XY: 722284

African (AFR) AF: 0.311 AC: 10351 AN: 33280

American (AMR) AF: 0.0473 AC: 2063 AN: 43608

Ashkenazi Jewish (ASJ) AF: 0.0607 AC: 1572 AN: 25884

East Asian (EAS) AF: 0.0722 AC: 2829 AN: 39198

South Asian (SAS) AF: 0.0342 AC: 2896 AN: 84632

European-Finnish (FIN) AF: 0.0281 AC: 1472 AN: 52448

Middle Eastern (MID) AF: 0.0664 AC: 382 AN: 5756

European-Non Finnish (NFE) AF: 0.0344 AC: 38158 AN: 1108516

Other (OTH) AF: 0.0594 AC: 3568 AN: 60038

GnomAD4 genome AF: 0.115 AC: 17443 AN: 152308 Hom.: 2043 Cov.: 34 AF XY: 0.113 AC XY: 8440 AN XY: 74478

African (AFR) AF: 0.303 AC: 12608 AN: 41546

American (AMR) AF: 0.0686 AC: 1050 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.0880 AC: 456 AN: 5184

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

European-Finnish (FIN) AF: 0.0297 AC: 316 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0348 AC: 2365 AN: 68024

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.0611 Hom.: 1017

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Methylmalonic acidemia due to transcobalamin receptor defect (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.10
DANN	Benign	0.67
PhyloP100		-2.6
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)		0.010		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: rs2232783; hg19: chr19-8368794;