Genetic Variant IMPACT:c.*2450G>A (chr18-24453297-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.24

Publications

11 publications found

Variant links:

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]

IMPACT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018439.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPACT	NM_018439.4	MANE Select	c.*2450G>A		3_prime_UTR	Exon 11 of 11	NP_060909.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IMPACT	ENST00000284202.9	TSL:1 MANE Select	c.*2450G>A	3_prime_UTR	Exon 11 of 11	ENSP00000284202.4
IMPACT	ENST00000580035.1	TSL:3	n.*233G>A	non_coding_transcript_exon	Exon 3 of 3	ENSP00000463710.1
IMPACT	ENST00000648078.1		c.*1868G>A	3_prime_UTR	Exon 12 of 12	ENSP00000497783.1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86194

AN:

151798

Hom.:

26182

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.638

AC:

1515

AN:

2374

AF XY:

0.639

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.568

AC:

86240

AN:

151916

Hom.:

26186

Cov.:

AF XY:

0.573

AC XY:

42556

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.333

AC:

13789

AN:

41406

American (AMR)

AF:

0.691

AC:

10568

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2496

AN:

3470

East Asian (EAS)

AF:

0.616

AC:

3173

AN:

5152

South Asian (SAS)

AF:

0.696

AC:

3350

AN:

4812

European-Finnish (FIN)

AF:

0.671

AC:

7061

AN:

10526

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.644

AC:

43736

AN:

67956

Other (OTH)

AF:

0.604

AC:

1274

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1754

3508

5263

7017

8771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.622

Hom.:

91565

Bravo

AF:

0.557

Asia WGS

AF:

0.632

AC:

2194

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over