Variant 5-39288709-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001737.5(C9):c.1645+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,477,496 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 101 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 54 hom. )

Consequence

C9
NM_001737.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.288

Variant links:

Genes affected

C9 (HGNC:1358): (complement C9) This gene encodes the final component of the complement system. It participates in the formation of the Membrane Attack Complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause component C9 deficiency. [provided by RefSeq, Feb 2009]

C9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-39288709-T-C is Benign according to our data. Variant chr5-39288709-T-C is described in ClinVar as [Benign]. Clinvar id is 1165576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-39288709-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C9	NM_001737.5 linkuse as main transcript	c.1645+14A>G		intron_variant		ENST00000263408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C9	ENST00000263408.5 linkuse as main transcript	c.1645+14A>G		intron_variant		1	NM_001737.5	P2

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2722

AN:

151862

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00527

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00473

AC:

1184

AN:

250126

Hom.:

AF XY:

0.00346

AC XY:

468

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.00294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000974

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00176

AC:

2331

AN:

1325516

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1006

AN XY:

667166

show subpopulations

Gnomad4 AFR exome

AF:

0.0643

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000168

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000384

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.0179

AC:

2723

AN:

151980

Hom.:

101

Cov.:

AF XY:

0.0173

AC XY:

1284

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.00526

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0150

Hom.:

Bravo

AF:

0.0202

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.3

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over