rs818714

Variant names:

• chr9-113421021-G-A
• rs818714
• NM_001278629.2:c.346-82G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C9orf43	NM_001278629.2	c.346-82G>A		intron_variant	Intron 4 of 13	ENST00000374165.6	NP_001265558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9orf43	ENST00000374165.6	c.346-82G>A		intron_variant	Intron 4 of 13	1	NM_001278629.2	ENSP00000363280.1
C9orf43	ENST00000288462.4	c.346-82G>A		intron_variant	Intron 4 of 13	1		ENSP00000288462.4
C9orf43	ENST00000490544.1	n.499-82G>A		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.393 AC: 8909 AN: 22682

American (AMR) AF: 0.171 AC: 6025 AN: 35246

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 5336 AN: 21182

East Asian (EAS) AF: 0.192 AC: 7039 AN: 36690

South Asian (SAS) AF: 0.300 AC: 21059 AN: 70228

European-Finnish (FIN) AF: 0.237 AC: 11458 AN: 48316

Middle Eastern (MID) AF: 0.243 AC: 1131 AN: 4646

European-Non Finnish (NFE) AF: 0.318 AC: 222014 AN: 699166

Other (OTH) AF: 0.294 AC: 12870 AN: 43752

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

African (AFR) AF: 0.396 AC: 16396 AN: 41440

American (AMR) AF: 0.242 AC: 3698 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3466

East Asian (EAS) AF: 0.176 AC: 911 AN: 5172

South Asian (SAS) AF: 0.320 AC: 1542 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2391 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20791 AN: 67928

Other (OTH) AF: 0.291 AC: 614 AN: 2110

Alfa AF: 0.308 Hom.: 9629

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
PhyloP100		-1.3
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: rs818714; hg19: chr9-116183301; COSMIC: COSV55913648;