rs7950395

Positions:

• chr11-44079568-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000263776.9(ACCS):​c.871C>T​(p.Leu291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,611,620 control chromosomes in the GnomAD database, including 11,136 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 0.12 (1137 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9999 hom.)
• Consequence: ACCS ENST00000263776.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

Genes affected

ACCS (HGNC:23989): (1-aminocyclopropane-1-carboxylate synthase homolog (inactive)) Enables identical protein binding activity. Predicted to be involved in biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=3.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACCS	NM_032592.4	c.871C>T	p.Leu291=	synonymous_variant	10/15	ENST00000263776.9	NP_115981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACCS	ENST00000263776.9	c.871C>T	p.Leu291=	synonymous_variant	10/15	1	NM_032592.4	ENSP00000263776	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18551 AN: 152072 Hom.: 1139 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.136

GnomAD3 exomes AF: 0.110 AC: 27148 AN: 247490 Hom.: 1618 AF XY: 0.111 AC XY: 14884 AN XY: 133586

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.0745

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.0944

Gnomad FIN exome AF: 0.0873

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.115 AC: 168105 AN: 1459430 Hom.: 9999 Cov.: 31 AF XY: 0.115 AC XY: 83548 AN XY: 725674

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0767

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.0979

Gnomad4 FIN exome AF: 0.0920

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.122 AC: 18551 AN: 152190 Hom.: 1137 Cov.: 32 AF XY: 0.122 AC XY: 9041 AN XY: 74410

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.134

Alfa AF: 0.120 Hom.: 846

Bravo AF: 0.123

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs7950395; hg19: chr11-44101118; COSMIC: COSV55460557; COSMIC: COSV55460557;