12-26069812-A-C

Variant names:

• chr12-26069812-A-C
• rs1546550
• NM_001394098.1:c.*994A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 3 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=-0.83).
• 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	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	c.*994A>C		3_prime_UTR_variant	Exon 6 of 6		NM_001394098.1	ENSP00000510086.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114636 AN: 152022 Hom.: 43875 Cov.: 33

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.: 37 AF XY: 0.785 AC XY: 301722 AN XY: 384212

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

GnomAD4 genome AF: 0.754 AC: 114705 AN: 152140 Hom.: 43898 Cov.: 33 AF XY: 0.746 AC XY: 55481 AN XY: 74364

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

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
DANN	Benign	0.63
PhyloP100		0.75
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: rs1546550; hg19: chr12-26222745; COSMIC: COSV109408805; COSMIC: COSV109408805;