rs1053474

Positions:

• chr18-24453297-G-A
• chr18-24453297-G-C

Variant summary

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

The NM_018439.4(IMPACT):​c.*2450G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,916 control chromosomes in the GnomAD database, including 26,186 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 0.57 (26186 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IMPACT NM_018439.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

Genes affected

IMPACT (HGNC:20387): (impact RWD domain protein) Predicted to enable actin binding activity and ribosome binding activity. Predicted to be involved in several processes, including GCN2-mediated signaling; cellular response to starvation; and negative regulation of nitrogen compound metabolic process. Predicted to be located in cytoplasm. Predicted to be part of polysome. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPACT	NM_018439.4	c.*2450G>A		3_prime_UTR_variant	11/11	ENST00000284202.9	NP_060909.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPACT	ENST00000284202.9	c.*2450G>A		3_prime_UTR_variant	11/11	1	NM_018439.4	ENSP00000284202	P1
IMPACT	ENST00000581278.1	c.*43G>A		3_prime_UTR_variant	4/4	2		ENSP00000463895
IMPACT	ENST00000648078.1	c.*1868G>A		3_prime_UTR_variant	12/12			ENSP00000497783
IMPACT	ENST00000580035.1	c.*233G>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	3		ENSP00000463710

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86194 AN: 151798 Hom.: 26182 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.638 AC: 1515 AN: 2374 Hom.: 483 AF XY: 0.639 AC XY: 694 AN XY: 1086

Gnomad ASJ exome AF: 1.00

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.750

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.568 AC: 86240 AN: 151916 Hom.: 26186 Cov.: 32 AF XY: 0.573 AC XY: 42556 AN XY: 74248

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.604

Alfa AF: 0.641 Hom.: 60804

Bravo AF: 0.557

Asia WGS AF: 0.632 AC: 2194 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.57

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: rs1053474; hg19: chr18-22033261;