5-39288709-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.1645+14A>G		intron_variant		ENST00000263408.5

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2722 AN: 151862 Hom.: 101 Cov.: 32

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.: 32 AF XY: 0.00346 AC XY: 468 AN XY: 135228

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.: 54 Cov.: 20 AF XY: 0.00151 AC XY: 1006 AN XY: 667166

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.: 32 AF XY: 0.0173 AC XY: 1284 AN XY: 74308

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.: 11

Bravo AF: 0.0202

Asia WGS AF: 0.00202 AC: 7 AN: 3476

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

Invitae

Jan 21, 2024

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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

Other links and lift over

dbSNP: rs700180; hg19: chr5-39288811;