rs2074038

Variant names:

• chr11-44066439-G-T
• rs2074038
• NM_032592.4:c.-263G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 53 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 -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 rank	MANE	Protein	UniProt
ACCS	NM_032592.4	c.-263G>T		5_prime_UTR_variant	Exon 1 of 15	ENST00000263776.9	NP_115981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACCS	ENST00000263776.9	c.-263G>T		5_prime_UTR_variant	Exon 1 of 15	1	NM_032592.4	ENSP00000263776.8

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.100 AC: 2 AN: 20

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.111 AC: 8 AN: 72

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0222 AC: 922 AN: 41584

American (AMR) AF: 0.0891 AC: 1363 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5168

South Asian (SAS) AF: 0.110 AC: 530 AN: 4824

European-Finnish (FIN) AF: 0.0767 AC: 814 AN: 10614

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7200 AN: 68018

Other (OTH) AF: 0.102 AC: 215 AN: 2114

Alfa AF: 0.0951 Hom.: 634

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
PhyloP100		0.10
PromoterAI		0.64	Over-expression
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2074038; hg19: chr11-44087989;