dbSNP rs11048399: RASSF8:c.*981G>A (chr12-26069799-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_001394098.1(RASSF8):c.*981G>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 0.0458 in 984,938 control chromosomes in the GnomAD database, including 1,264 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 0.065 ( 444 hom., cov: 33)

Exomes 𝑓: 0.042 ( 820 hom. )

Consequence

RASSF8
NM_001394098.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.589

Publications

4 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF8	NM_001394098.1 link	c.*981G>A		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.*981G>A		3_prime_UTR_variant	Exon 6 of 6		NM_001394098.1	ENSP00000510086.1		Q8NHQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0646

AC:

9823

AN:

152140

Hom.:

441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0526

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0717

GnomAD4 exome

AF:

0.0424

AC:

35325

AN:

832680

Hom.:

820

Cov.:

AF XY:

0.0422

AC XY:

16217

AN XY:

384538

show subpopulations

African (AFR)

AF:

0.138

AC:

2179

AN:

15766

American (AMR)

AF:

0.0376

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

327

AN:

5154

East Asian (EAS)

AF:

0.00854

AC:

AN:

3630

South Asian (SAS)

AF:

0.0328

AC:

539

AN:

16456

European-Finnish (FIN)

AF:

0.0399

AC:

AN:

276

Middle Eastern (MID)

AF:

0.0914

AC:

148

AN:

1620

European-Non Finnish (NFE)

AF:

0.0405

AC:

30869

AN:

761510

Other (OTH)

AF:

0.0434

AC:

1184

AN:

27284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1706

3412

5118

6824

8530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1666

3332

4998

6664

8330

<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:

0.0646

AC:

9833

AN:

152258

Hom.:

444

Cov.:

AF XY:

0.0639

AC XY:

4757

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.126

AC:

5251

AN:

41544

American (AMR)

AF:

0.0460

AC:

703

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0562

AC:

195

AN:

3468

East Asian (EAS)

AF:

0.0108

AC:

AN:

5192

South Asian (SAS)

AF:

0.0297

AC:

143

AN:

4820

European-Finnish (FIN)

AF:

0.0526

AC:

558

AN:

10602

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0402

AC:

2731

AN:

68014

Other (OTH)

AF:

0.0724

AC:

153

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

463

925

1388

1850

2313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0513

Hom.:

468

Bravo

AF:

0.0663

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.16

(source)

DANN

Benign

0.51

PhyloP100

-0.59

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