rs4844390

Variant names:

• chr1-207761504-A-G
• rs4844390
• NM_172351.3:c.673+58A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172351.3(CD46):​c.673+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,402,798 control chromosomes in the GnomAD database, including 30,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2383 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28267 hom.)
• Consequence: CD46 NM_172351.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.15
• Publications: 13 publications found

Genes affected

CD46 (HGNC:6953): (CD46 molecule) The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. Mutations at this locus have been associated with susceptibility to hemolytic uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]

MIR29B2CHG (HGNC:32018): (MIR29B2 and MIR29C host gene)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-207761504-A-G is Benign according to our data. Variant chr1-207761504-A-G is described in ClinVar as Benign. ClinVar VariationId is 1181135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172351.3. 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
	CD46	NM_172351.3	MANE Select	c.673+58A>G		intron	N/A	NP_758861.1	P15529-11
	CD46	NM_172359.3		c.673+58A>G		intron	N/A	NP_758869.1	P15529-2
	CD46	NM_002389.4		c.673+58A>G		intron	N/A	NP_002380.3	P15529-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD46	ENST00000367042.6	TSL:1 MANE Select	c.673+58A>G		intron	N/A	ENSP00000356009.1	P15529-11
	CD46	ENST00000322875.8	TSL:1	c.673+58A>G		intron	N/A	ENSP00000313875.4	P15529-2
	CD46	ENST00000358170.6	TSL:1	c.673+58A>G		intron	N/A	ENSP00000350893.2	P15529-1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24100 AN: 152100 Hom.: 2377 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00672

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.204 AC: 255114 AN: 1250580 Hom.: 28267 AF XY: 0.202 AC XY: 127792 AN XY: 631746

African (AFR) AF: 0.0463 AC: 1365 AN: 29470

American (AMR) AF: 0.280 AC: 12297 AN: 43842

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3225 AN: 24658

East Asian (EAS) AF: 0.00432 AC: 167 AN: 38636

South Asian (SAS) AF: 0.165 AC: 13407 AN: 81172

European-Finnish (FIN) AF: 0.218 AC: 11156 AN: 51194

Middle Eastern (MID) AF: 0.118 AC: 634 AN: 5352

European-Non Finnish (NFE) AF: 0.220 AC: 203433 AN: 922916

Other (OTH) AF: 0.177 AC: 9430 AN: 53340

GnomAD4 genome AF: 0.158 AC: 24102 AN: 152218 Hom.: 2383 Cov.: 32 AF XY: 0.158 AC XY: 11747 AN XY: 74402

African (AFR) AF: 0.0537 AC: 2231 AN: 41544

American (AMR) AF: 0.223 AC: 3416 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3472

East Asian (EAS) AF: 0.00655 AC: 34 AN: 5194

South Asian (SAS) AF: 0.145 AC: 700 AN: 4826

European-Finnish (FIN) AF: 0.221 AC: 2332 AN: 10564

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14496 AN: 67998

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.190 Hom.: 693

Bravo AF: 0.155

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Atypical hemolytic-uremic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.86
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs4844390; hg19: chr1-207934849; COSMIC: COSV59736263; COSMIC: COSV59736263;