rs2074038

Positions:

• chr11-44066439-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032592.4(ACCS):​c.-263G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 152,402 control chromosomes in the GnomAD database, including 856 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 0.087 (855 hom., cov: 33)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: ACCS NM_032592.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACCS	NM_032592.4	c.-263G>T		5_prime_UTR_variant	1/15	ENST00000263776.9	NP_115981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACCS	ENST00000263776.9	c.-263G>T		5_prime_UTR_variant	1/15	1	NM_032592.4	ENSP00000263776	P1
ACCS	ENST00000524990.5	c.-1+117G>T		intron_variant		4		ENSP00000434156
ACCS	ENST00000533208.5	n.88+427G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13294 AN: 152184 Hom.: 856 Cov.: 33

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.100 AC: 10 AN: 100 Hom.: 1 Cov.: 0 AF XY: 0.0875 AC XY: 7 AN XY: 80

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0872 AC: 13288 AN: 152302 Hom.: 855 Cov.: 33 AF XY: 0.0885 AC XY: 6590 AN XY: 74472

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0767

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0993 Hom.: 335

Bravo AF: 0.0900

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs2074038; hg19: chr11-44087989;