9-74948171-C-T

Variant names:

• chr9-74948171-C-T
• rs2769058
• NM_017998.3:c.462G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_017998.3(C9orf40):​c.462G>A​(p.Gln154Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,611,594 control chromosomes in the GnomAD database, including 86,003 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 (7173 hom., cov: 32)
  • Exomes 𝑓: 0.33 (78830 hom.)
• Consequence: C9orf40 NM_017998.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989
• Publications: 20 publications found

Genes affected

C9orf40 (HGNC:23433): (chromosome 9 open reading frame 40)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.989 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9orf40	NM_017998.3	c.462G>A	p.Gln154Gln	synonymous_variant	Exon 2 of 2	ENST00000376854.6	NP_060468.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9orf40	ENST00000376854.6	c.462G>A	p.Gln154Gln	synonymous_variant	Exon 2 of 2	1	NM_017998.3	ENSP00000366050.5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46340 AN: 151808 Hom.: 7168 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.329

GnomAD2 exomes AF: 0.321 AC: 80278 AN: 250252 AF XY: 0.323

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.309

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.365

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.327 AC: 477465 AN: 1459668 Hom.: 78830 Cov.: 31 AF XY: 0.327 AC XY: 237310 AN XY: 726232

African (AFR) AF: 0.254 AC: 8475 AN: 33430

American (AMR) AF: 0.310 AC: 13876 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8351 AN: 26114

East Asian (EAS) AF: 0.383 AC: 15174 AN: 39658

South Asian (SAS) AF: 0.322 AC: 27779 AN: 86198

European-Finnish (FIN) AF: 0.310 AC: 16529 AN: 53400

Middle Eastern (MID) AF: 0.354 AC: 2044 AN: 5766

European-Non Finnish (NFE) AF: 0.329 AC: 365328 AN: 1110086

Other (OTH) AF: 0.330 AC: 19909 AN: 60316

GnomAD4 genome AF: 0.305 AC: 46358 AN: 151926 Hom.: 7173 Cov.: 32 AF XY: 0.307 AC XY: 22780 AN XY: 74234

African (AFR) AF: 0.255 AC: 10563 AN: 41434

American (AMR) AF: 0.326 AC: 4980 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3468

East Asian (EAS) AF: 0.382 AC: 1967 AN: 5154

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4816

European-Finnish (FIN) AF: 0.311 AC: 3274 AN: 10518

Middle Eastern (MID) AF: 0.328 AC: 95 AN: 290

European-Non Finnish (NFE) AF: 0.320 AC: 21771 AN: 67968

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.319 Hom.: 30594

Bravo AF: 0.304

Asia WGS AF: 0.329 AC: 1142 AN: 3478

EpiCase AF: 0.324

EpiControl AF: 0.340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.5
DANN	Benign	0.72
PhyloP100		0.99
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2769058; hg19: chr9-77563087; COSMIC: COSV65228427; COSMIC: COSV65228427;