rs2227288

Variant names:

• chr19-8302641-G-C
• rs2227288
• NM_016579.4:c.707-36C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-8302641-G-C
• chr19-8302641-G-A
• chr19-8302641-G-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.707-36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,608,938 control chromosomes in the GnomAD database, including 12,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1689 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10592 hom.)
• Consequence: CD320 NM_016579.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.555
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-8302641-G-C is Benign according to our data. Variant chr19-8302641-G-C is described in ClinVar as Benign. ClinVar VariationId is 1248253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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.707-36C>G		intron	N/A	NP_057663.1	Q9NPF0-1
	CD320	NM_001165895.2		c.581-36C>G		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.707-36C>G		intron	N/A	ENSP00000301458.4	Q9NPF0-1
	CD320	ENST00000596002.5	TSL:1	n.*995-36C>G		intron	N/A	ENSP00000471773.1	M0R1C4
	CD320	ENST00000963189.1		c.1019-36C>G		intron	N/A	ENSP00000633248.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21413 AN: 151976 Hom.: 1689 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.121 AC: 29892 AN: 247986 AF XY: 0.121

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0721

Gnomad FIN exome AF: 0.0611

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.117 AC: 170128 AN: 1456844 Hom.: 10592 Cov.: 34 AF XY: 0.117 AC XY: 84762 AN XY: 723826

African (AFR) AF: 0.207 AC: 6908 AN: 33352

American (AMR) AF: 0.119 AC: 5312 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3994 AN: 26020

East Asian (EAS) AF: 0.0693 AC: 2744 AN: 39574

South Asian (SAS) AF: 0.108 AC: 9292 AN: 86156

European-Finnish (FIN) AF: 0.0645 AC: 3411 AN: 52888

Middle Eastern (MID) AF: 0.197 AC: 1129 AN: 5740

European-Non Finnish (NFE) AF: 0.117 AC: 129876 AN: 1108412

Other (OTH) AF: 0.124 AC: 7462 AN: 60104

GnomAD4 genome AF: 0.141 AC: 21427 AN: 152094 Hom.: 1689 Cov.: 32 AF XY: 0.139 AC XY: 10309 AN XY: 74358

African (AFR) AF: 0.205 AC: 8491 AN: 41456

American (AMR) AF: 0.133 AC: 2034 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3470

East Asian (EAS) AF: 0.0678 AC: 351 AN: 5174

South Asian (SAS) AF: 0.0922 AC: 445 AN: 4828

European-Finnish (FIN) AF: 0.0602 AC: 638 AN: 10598

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8476 AN: 67972

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.134 Hom.: 266

Bravo AF: 0.152

Asia WGS AF: 0.0870 AC: 301 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	-0.85
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2227288; hg19: chr19-8367525; COSMIC: COSV56848128; COSMIC: COSV56848128;