chr12-26052446-G-A

Variant names:

• chr12-26052446-G-A
• rs1513126
• NM_001394098.1:c.-108-2790G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394098.1(RASSF8):​c.-108-2790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,160 control chromosomes in the GnomAD database, including 49,635 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 0.81 (49635 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RASSF8 NM_001394098.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF8	NM_001394098.1	c.-108-2790G>A		intron_variant	Intron 2 of 5	ENST00000689635.1	NP_001381027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF8	ENST00000689635.1	c.-108-2790G>A		intron_variant	Intron 2 of 5		NM_001394098.1	ENSP00000510086.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122540 AN: 152042 Hom.: 49603 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.809

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122623 AN: 152160 Hom.: 49635 Cov.: 32 AF XY: 0.812 AC XY: 60394 AN XY: 74386

African (AFR) AF: 0.738 AC: 30611 AN: 41486

American (AMR) AF: 0.850 AC: 12992 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2563 AN: 3470

East Asian (EAS) AF: 0.937 AC: 4852 AN: 5180

South Asian (SAS) AF: 0.916 AC: 4416 AN: 4820

European-Finnish (FIN) AF: 0.829 AC: 8780 AN: 10586

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.818 AC: 55653 AN: 68014

Other (OTH) AF: 0.811 AC: 1712 AN: 2110

Alfa AF: 0.812 Hom.: 70579

Bravo AF: 0.804

Asia WGS AF: 0.902 AC: 3137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.66
PhyloP100		0.68
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1513126; hg19: chr12-26205379; COSMIC: COSV99281038; COSMIC: COSV99281038;