5-39315643-G-T

Variant names:

• chr5-39315643-G-T
• rs187875
• NM_001737.5:c.870+132C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001737.5(C9):​c.870+132C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 526,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• complement component 9 deficiency

  Inheritance: AR, Unknown Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001737.5. 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
	C9	NM_001737.5	MANE Select	c.870+132C>A		intron	N/A	NP_001728.1	P02748

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C9	ENST00000263408.5	TSL:1 MANE Select	c.870+132C>A		intron	N/A	ENSP00000263408.4	P02748
	C9	ENST00000884641.1		c.954+132C>A		intron	N/A	ENSP00000554700.1
	C9	ENST00000884639.1		c.870+132C>A		intron	N/A	ENSP00000554698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000190 AC: 1 AN: 526096 Hom.: 0 AF XY: 0.00000363 AC XY: 1 AN XY: 275856

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13654

American (AMR) AF: 0.00 AC: 0 AN: 19434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14970

East Asian (EAS) AF: 0.00 AC: 0 AN: 31294

South Asian (SAS) AF: 0.00 AC: 0 AN: 45882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2126

European-Non Finnish (NFE) AF: 0.00000300 AC: 1 AN: 333430

Other (OTH) AF: 0.00 AC: 0 AN: 28322

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.016
DANN	Benign	0.32
PhyloP100		-1.9

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: rs187875; hg19: chr5-39315745;