rs11048399

chr12-26069799-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RASSF8	NM_001394098.1	c.*981G>A		3_prime_UTR_variant	6/6	ENST00000689635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF8	ENST00000689635.1	c.*981G>A		3_prime_UTR_variant	6/6		NM_001394098.1	P1

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9823 AN: 152140 Hom.: 441 Cov.: 33

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.: 29 AF XY: 0.0422 AC XY: 16217 AN XY: 384538

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0376

Gnomad4 ASJ exome AF: 0.0634

Gnomad4 EAS exome AF: 0.00854

Gnomad4 SAS exome AF: 0.0328

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0405

Gnomad4 OTH exome AF: 0.0434

GnomAD4 genome AF: 0.0646 AC: 9833 AN: 152258 Hom.: 444 Cov.: 33 AF XY: 0.0639 AC XY: 4757 AN XY: 74442

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0460

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.0297

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0402

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0562 Hom.: 93

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
Dann	Benign	0.51

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: rs11048399; hg19: chr12-26222732;