11-44077852-G-A

Variant names:

• chr11-44077852-G-A
• rs35514614
• NM_032592.4:c.662G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032592.4(ACCS):​c.662G>A​(p.Gly221Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00204 in 1,613,802 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G221W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (26 hom.)
• Consequence: ACCS NM_032592.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.74
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034445226).
• BP6: Variant 11-44077852-G-A is Benign according to our data. Variant chr11-44077852-G-A is described in ClinVar as Benign. ClinVar VariationId is 712076.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00638 (972/152260) while in subpopulation AFR AF = 0.02 (831/41534). AF 95% confidence interval is 0.0189. There are 8 homozygotes in GnomAd4. There are 500 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.662G>A	p.Gly221Glu	missense	Exon 8 of 15	NP_115981.1	A0A0S2Z622
	ACCS	NM_001127219.2		c.662G>A	p.Gly221Glu	missense	Exon 8 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.662G>A	p.Gly221Glu	missense	Exon 8 of 15	ENSP00000263776.8	Q96QU6-1
	ACCS	ENST00000894384.1		c.662G>A	p.Gly221Glu	missense	Exon 8 of 15	ENSP00000564443.1
	ACCS	ENST00000964372.1		c.662G>A	p.Gly221Glu	missense	Exon 8 of 15	ENSP00000634431.1

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 966 AN: 152142 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00353 AC: 885 AN: 250886 AF XY: 0.00367

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00614

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00159 AC: 2326 AN: 1461542 Hom.: 26 Cov.: 32 AF XY: 0.00184 AC XY: 1340 AN XY: 727056

African (AFR) AF: 0.0206 AC: 690 AN: 33478

American (AMR) AF: 0.000873 AC: 39 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00856 AC: 340 AN: 39698

South Asian (SAS) AF: 0.0108 AC: 934 AN: 86180

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53396

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5760

European-Non Finnish (NFE) AF: 0.000111 AC: 123 AN: 1111854

Other (OTH) AF: 0.00296 AC: 179 AN: 60380

GnomAD4 genome AF: 0.00638 AC: 972 AN: 152260 Hom.: 8 Cov.: 32 AF XY: 0.00672 AC XY: 500 AN XY: 74446

African (AFR) AF: 0.0200 AC: 831 AN: 41534

American (AMR) AF: 0.00150 AC: 23 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00792 AC: 41 AN: 5174

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00254 Hom.: 10

Bravo AF: 0.00663

ESP6500AA AF: 0.0193 AC: 85

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00392 AC: 476

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.59
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.83	L
PhyloP100		4.7
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.065
Sift	Benign	0.92	T
Sift4G	Benign	0.59	T
Polyphen		0.0050	B
Vest4		0.28
MVP		0.75
MPC		0.15
ClinPred		0.013	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.35
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs35514614; hg19: chr11-44099402; COSMIC: COSV55458903; COSMIC: COSV55458903;