rs2232785

Positions:

• chr19-8303737-C-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.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

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=-0.89).
• BP6: Variant 19-8303737-C-T is Benign according to our data. Variant chr19-8303737-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD320	NM_016579.4	c.502+118G>A		intron_variant		ENST00000301458.10
CD320	NM_001165895.2	c.376+118G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD320	ENST00000301458.10	c.502+118G>A		intron_variant		1	NM_016579.4	P1
CD320	ENST00000596002.5	c.*790+118G>A		intron_variant, NMD_transcript_variant		1
CD320	ENST00000537716.6	c.376+118G>A		intron_variant		2
CD320	ENST00000599573.1	c.*102+118G>A		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0489

Gnomad4 ASJ exome AF: 0.0607

Gnomad4 EAS exome AF: 0.0691

Gnomad4 SAS exome AF: 0.0341

Gnomad4 FIN exome AF: 0.0286

Gnomad4 NFE exome AF: 0.0334

Gnomad4 OTH exome AF: 0.0619

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

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0348

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0826 Hom.: 137

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 286 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

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs2232785; hg19: chr19-8368621; COSMIC: COSV56847985; COSMIC: COSV56847985;