rs2227288

chr19-8302641-G-Cchr19-8302641-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.555

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1248253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD320	NM_016579.4	c.707-36C>G		intron_variant		ENST00000301458.10
CD320	NM_001165895.2	c.581-36C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD320	ENST00000301458.10	c.707-36C>G		intron_variant		1	NM_016579.4	P1
CD320	ENST00000596002.5	c.*995-36C>G		intron_variant, NMD_transcript_variant		1
CD320	ENST00000537716.6	c.581-36C>G		intron_variant		2
CD320	ENST00000599573.1	c.*307-36C>G		intron_variant, NMD_transcript_variant		2

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

GnomAD3 exomes AF: 0.121 AC: 29892 AN: 247986 Hom.: 1924 AF XY: 0.121 AC XY: 16254 AN XY: 134158

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 SAS exome AF: 0.109

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

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.0693

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0645

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.124

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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.147

Alfa AF: 0.134 Hom.: 266

Bravo AF: 0.152

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.20
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227288; hg19: chr19-8367525; COSMIC: COSV56848128; COSMIC: COSV56848128;