NM_172351.3:c.*1435T>C

Variant names:

• chr1-207794912-T-C
• rs14374
• NM_172351.3:c.*1435T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_172351.3(CD46):​c.*1435T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 152,354 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (102 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CD46 NM_172351.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35
• Publications: 12 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=-0.89).
• BP6: Variant 1-207794912-T-C is Benign according to our data. Variant chr1-207794912-T-C is described in ClinVar as Benign. ClinVar VariationId is 294989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0316 (4821/152354) while in subpopulation NFE AF = 0.0487 (3313/68034). AF 95% confidence interval is 0.0473. There are 102 homozygotes in GnomAd4. There are 2271 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 102 AD,AR,SD gene

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.*1435T>C		3_prime_UTR	Exon 13 of 13	NP_758861.1	P15529-11
	CD46	NM_172359.3		c.*1321T>C		3_prime_UTR	Exon 13 of 13	NP_758869.1	P15529-2
	CD46	NM_002389.4		c.*1435T>C		3_prime_UTR	Exon 14 of 14	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.*1435T>C		3_prime_UTR	Exon 13 of 13	ENSP00000356009.1	P15529-11
	CD46	ENST00000322875.8	TSL:1	c.*1321T>C		3_prime_UTR	Exon 13 of 13	ENSP00000313875.4	P15529-2
	CD46	ENST00000358170.6	TSL:1	c.*1435T>C		3_prime_UTR	Exon 14 of 14	ENSP00000350893.2	P15529-1

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4821 AN: 152236 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00793

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0296

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0316 AC: 4821 AN: 152354 Hom.: 102 Cov.: 32 AF XY: 0.0305 AC XY: 2271 AN XY: 74500

African (AFR) AF: 0.00791 AC: 329 AN: 41594

American (AMR) AF: 0.0284 AC: 435 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0405 AC: 195 AN: 4818

European-Finnish (FIN) AF: 0.0362 AC: 384 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3313 AN: 68034

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0391 Hom.: 153

Bravo AF: 0.0288

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs14374; hg19: chr1-207968257;