dbSNP rs1546550: RASSF8:c.*994A>C (chr12-26069812-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001394098.1(RASSF8):c.*994A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 984,126 control chromosomes in the GnomAD database, including 300,557 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 0.75 ( 43898 hom., cov: 33)

Exomes 𝑓: 0.78 ( 256659 hom. )

Consequence

RASSF8
NM_001394098.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.753

Publications

3 publications found

Variant links:

Genes affected

RASSF8 (HGNC:13232): (Ras association domain family member 8) This gene encodes a member of the Ras-assocation domain family (RASSF) of tumor suppressor proteins. This gene is essential for maintaining adherens junction function in epithelial cells and has a role in epithelial cell migration. It is a lung tumor suppressor gene candidate. A chromosomal translocation t(12;22)(p11.2;q13.3) leading to the fusion of this gene and the FBLN1 gene is found in a complex type of synpolydactyly. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

RASSF8 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF8	NM_001394098.1 link	c.*994A>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000689635.1	NP_001381027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF8	ENST00000689635.1 link	c.*994A>C		3_prime_UTR_variant	Exon 6 of 6		NM_001394098.1	ENSP00000510086.1		Q8NHQ8-1

Frequencies

GnomAD3 genomes

AF:

0.754

AC:

114636

AN:

152022

Hom.:

43875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.810

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.745

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.780

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.780

Gnomad OTH

AF:

0.753

GnomAD4 exome

AF:

0.785

AC:

652941

AN:

831986

Hom.:

256659

Cov.:

AF XY:

0.785

AC XY:

301722

AN XY:

384212

show subpopulations

African (AFR)

AF:

0.822

AC:

12952

AN:

15754

American (AMR)

AF:

0.522

AC:

513

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

3755

AN:

5152

East Asian (EAS)

AF:

0.501

AC:

1819

AN:

3628

South Asian (SAS)

AF:

0.627

AC:

10309

AN:

16444

European-Finnish (FIN)

AF:

0.779

AC:

215

AN:

276

Middle Eastern (MID)

AF:

0.784

AC:

1270

AN:

1620

European-Non Finnish (NFE)

AF:

0.790

AC:

601213

AN:

760866

Other (OTH)

AF:

0.766

AC:

20895

AN:

27264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

7434

14868

22303

29737

37171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19340

38680

58020

77360

96700

<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:

0.754

AC:

114705

AN:

152140

Hom.:

43898

Cov.:

AF XY:

0.746

AC XY:

55481

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.810

AC:

33623

AN:

41530

American (AMR)

AF:

0.582

AC:

8887

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.745

AC:

2586

AN:

3470

East Asian (EAS)

AF:

0.525

AC:

2722

AN:

5182

South Asian (SAS)

AF:

0.628

AC:

3030

AN:

4824

European-Finnish (FIN)

AF:

0.780

AC:

8248

AN:

10578

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.780

AC:

53022

AN:

67978

Other (OTH)

AF:

0.750

AC:

1585

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1402

2804

4207

5609

7011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.764

Hom.:

15243

Bravo

AF:

0.743

Asia WGS

AF:

0.609

AC:

2119

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.63

PhyloP100

0.75

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