5-39328404-A-G

Variant names:

• chr5-39328404-A-G
• rs261752
• NM_001737.5:c.615+3272T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001737.5(C9):​c.615+3272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,018 control chromosomes in the GnomAD database, including 20,570 homozygotes. 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: 𝑓 0.51 (20570 hom., cov: 32)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 11 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: Unknown, AR Classification: STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9	NM_001737.5	c.615+3272T>C		intron_variant	Intron 5 of 10	ENST00000263408.5	NP_001728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9	ENST00000263408.5	c.615+3272T>C		intron_variant	Intron 5 of 10	1	NM_001737.5	ENSP00000263408.4

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77205 AN: 151900 Hom.: 20535 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.468

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77283 AN: 152018 Hom.: 20570 Cov.: 32 AF XY: 0.504 AC XY: 37495 AN XY: 74330

African (AFR) AF: 0.685 AC: 28380 AN: 41456

American (AMR) AF: 0.442 AC: 6759 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2434 AN: 5166

South Asian (SAS) AF: 0.432 AC: 2086 AN: 4824

European-Finnish (FIN) AF: 0.472 AC: 4996 AN: 10574

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30005 AN: 67938

Other (OTH) AF: 0.466 AC: 983 AN: 2110

Alfa AF: 0.461 Hom.: 55890

Bravo AF: 0.518

Asia WGS AF: 0.444 AC: 1542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.40
PhyloP100		-0.37
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: rs261752; hg19: chr5-39328506;