rs818714

Positions:

• chr9-113421021-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278629.2(C9orf43):​c.346-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,133,892 control chromosomes in the GnomAD database, including 53,234 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 0.31 (7683 hom., cov: 32)
  • Exomes 𝑓: 0.30 (45551 hom.)
• Consequence: C9orf43 NM_001278629.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

Genes affected

C9orf43 (HGNC:23570): (chromosome 9 open reading frame 43)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C9orf43	NM_001278629.2	c.346-82G>A		intron_variant		ENST00000374165.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C9orf43	ENST00000374165.6	c.346-82G>A		intron_variant		1	NM_001278629.2	P1
C9orf43	ENST00000288462.4	c.346-82G>A		intron_variant		1		P1
C9orf43	ENST00000490544.1	n.499-82G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47551 AN: 151866 Hom.: 7678 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.301 AC: 295841 AN: 981908 Hom.: 45551 AF XY: 0.302 AC XY: 152153 AN XY: 504398

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.313 AC: 47584 AN: 151984 Hom.: 7683 Cov.: 32 AF XY: 0.308 AC XY: 22858 AN XY: 74292

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.291

Alfa AF: 0.306 Hom.: 7349

Bravo AF: 0.315

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.040
DANN	Benign	0.42

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: rs818714; hg19: chr9-116183301; COSMIC: COSV55913648;