rs7950395

Variant names:

• chr11-44079568-C-T
• rs7950395
• NM_032592.4:c.871C>T

Variant summary

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

The NM_032592.4(ACCS):​c.871C>T​(p.Leu291Leu) 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 NM_032592.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCS	NM_032592.4	MANE Select	c.871C>T	p.Leu291Leu	synonymous	Exon 10 of 15	NP_115981.1	A0A0S2Z622
	ACCS	NM_001127219.2		c.871C>T	p.Leu291Leu	synonymous	Exon 10 of 15	NP_001120691.1	A0A0S2Z622

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCS	ENST00000263776.9	TSL:1 MANE Select	c.871C>T	p.Leu291Leu	synonymous	Exon 10 of 15	ENSP00000263776.8	Q96QU6-1
	ACCS	ENST00000894384.1		c.871C>T	p.Leu291Leu	synonymous	Exon 10 of 15	ENSP00000564443.1
	ACCS	ENST00000964372.1		c.871C>T	p.Leu291Leu	synonymous	Exon 10 of 15	ENSP00000634431.1

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

GnomAD2 exomes AF: 0.110 AC: 27148 AN: 247490 AF XY: 0.111

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 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

African (AFR) AF: 0.134 AC: 4470 AN: 33452

American (AMR) AF: 0.0767 AC: 3420 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3125 AN: 26110

East Asian (EAS) AF: 0.107 AC: 4261 AN: 39682

South Asian (SAS) AF: 0.0979 AC: 8372 AN: 85528

European-Finnish (FIN) AF: 0.0920 AC: 4909 AN: 53342

Middle Eastern (MID) AF: 0.162 AC: 863 AN: 5318

European-Non Finnish (NFE) AF: 0.118 AC: 131355 AN: 1111108

Other (OTH) AF: 0.122 AC: 7330 AN: 60310

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

African (AFR) AF: 0.134 AC: 5545 AN: 41496

American (AMR) AF: 0.104 AC: 1591 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3470

East Asian (EAS) AF: 0.111 AC: 573 AN: 5178

South Asian (SAS) AF: 0.0965 AC: 465 AN: 4820

European-Finnish (FIN) AF: 0.0959 AC: 1018 AN: 10616

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8443 AN: 68002

Other (OTH) AF: 0.134 AC: 282 AN: 2112

Alfa AF: 0.120 Hom.: 948

Bravo AF: 0.123

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		3.0
Mutation Taster		=93/7	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: rs7950395; hg19: chr11-44101118; COSMIC: COSV55460557; COSMIC: COSV55460557;