rs250511

Variant names:

• chr19-8302620-T-A
• rs250511
• NM_016579.4:c.707-15A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-8302620-T-A
• chr19-8302620-T-C

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.707-15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,611,924 control chromosomes in the GnomAD database, including 7,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (661 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7069 hom.)
• Consequence: CD320 NM_016579.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.07
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-8302620-T-A is Benign according to our data. Variant chr19-8302620-T-A is described in ClinVar as Benign. ClinVar VariationId is 136685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4	c.707-15A>T		intron_variant	Intron 4 of 4	ENST00000301458.10	NP_057663.1
CD320	NM_001165895.2	c.581-15A>T		intron_variant	Intron 3 of 3		NP_001159367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10	c.707-15A>T		intron_variant	Intron 4 of 4	1	NM_016579.4	ENSP00000301458.4
CD320	ENST00000596002.5	n.*995-15A>T		intron_variant	Intron 4 of 4	1		ENSP00000471773.1
CD320	ENST00000537716.6	c.581-15A>T		intron_variant	Intron 3 of 3	2		ENSP00000437697.1
CD320	ENST00000599573.1	n.*307-15A>T		intron_variant	Intron 4 of 4	2		ENSP00000471551.1

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13411 AN: 151938 Hom.: 662 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.0948

GnomAD2 exomes AF: 0.0886 AC: 22092 AN: 249236 AF XY: 0.0902

Gnomad AFR exome AF: 0.0750

Gnomad AMR exome AF: 0.0414

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.0895

Gnomad NFE exome AF: 0.0936

Gnomad OTH exome AF: 0.0922

GnomAD4 exome AF: 0.0962 AC: 140429 AN: 1459868 Hom.: 7069 Cov.: 34 AF XY: 0.0962 AC XY: 69850 AN XY: 725918

African (AFR) AF: 0.0809 AC: 2704 AN: 33440

American (AMR) AF: 0.0443 AC: 1979 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4057 AN: 26078

East Asian (EAS) AF: 0.140 AC: 5546 AN: 39648

South Asian (SAS) AF: 0.0774 AC: 6678 AN: 86224

European-Finnish (FIN) AF: 0.0901 AC: 4779 AN: 53032

Middle Eastern (MID) AF: 0.126 AC: 728 AN: 5758

European-Non Finnish (NFE) AF: 0.0972 AC: 107948 AN: 1110730

Other (OTH) AF: 0.0997 AC: 6010 AN: 60280

GnomAD4 genome AF: 0.0883 AC: 13419 AN: 152056 Hom.: 661 Cov.: 32 AF XY: 0.0872 AC XY: 6481 AN XY: 74326

African (AFR) AF: 0.0754 AC: 3126 AN: 41468

American (AMR) AF: 0.0662 AC: 1011 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5162

South Asian (SAS) AF: 0.0830 AC: 400 AN: 4820

European-Finnish (FIN) AF: 0.0858 AC: 908 AN: 10586

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6372 AN: 67960

Other (OTH) AF: 0.0948 AC: 200 AN: 2110

Alfa AF: 0.0682 Hom.: 119

Bravo AF: 0.0867

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Sep 09, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Methylmalonic acidemia due to transcobalamin receptor defect Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.51
PhyloP100		-1.1
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: rs250511; hg19: chr19-8367504; COSMIC: COSV56848443; COSMIC: COSV56848443;