Genetic Variant NM_015193.5:c.*742+58G>A (chr8-142612050-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015193.5(ARC):c.*742+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,740 control chromosomes in the GnomAD database, including 6,030 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 0.27 ( 6010 hom., cov: 33)

Exomes 𝑓: 0.22 ( 20 hom. )

Consequence

ARC
NM_015193.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.242

Publications

6 publications found

Variant links:

Genes affected

ARC (HGNC:648): (activity regulated cytoskeleton associated protein) Predicted to enable mRNA binding activity. Involved in cell migration; cytoskeleton organization; and regulation of cell morphogenesis. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARC 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARC	NM_015193.5 link	c.*742+58G>A		intron_variant	Intron 2 of 2	ENST00000356613.4	NP_056008.1	Q7LC44
ARC	NM_001412852.1 link	c.*800G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001399781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARC	ENST00000356613.4 link	c.*742+58G>A		intron_variant	Intron 2 of 2	1	NM_015193.5	ENSP00000349022.2		Q7LC44
ARC	ENST00000581404.1 link	n.*15G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41512

AN:

151858

Hom.:

6012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.220

AC:

168

AN:

764

Hom.:

Cov.:

AF XY:

0.209

AC XY:

106

AN XY:

508

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.222

AC:

AN:

446

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.213

AC:

AN:

254

Other (OTH)

AF:

0.308

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.273

AC:

41548

AN:

151976

Hom.:

6010

Cov.:

AF XY:

0.273

AC XY:

20291

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.362

AC:

15003

AN:

41448

American (AMR)

AF:

0.224

AC:

3417

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1220

AN:

3468

East Asian (EAS)

AF:

0.194

AC:

997

AN:

5142

South Asian (SAS)

AF:

0.293

AC:

1408

AN:

4810

European-Finnish (FIN)

AF:

0.210

AC:

2218

AN:

10572

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.239

AC:

16215

AN:

67940

Other (OTH)

AF:

0.274

AC:

579

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1488

2976

4465

5953

7441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.147

Hom.:

307

Bravo

AF:

0.276

Asia WGS

AF:

0.233

AC:

815

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.0

(source)

DANN

Benign

0.82

PhyloP100

-0.24

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over