rs1546550

Positions:

• chr12-26069812-A-C
• chr12-26069812-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	UniProt
RASSF8	NM_001394098.1	c.*994A>C		3_prime_UTR_variant	6/6	ENST00000689635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF8	ENST00000689635.1	c.*994A>C		3_prime_UTR_variant	6/6		NM_001394098.1	P1

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

Gnomad4 AFR exome AF: 0.822

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.779

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.766

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

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.750

Alfa AF: 0.766 Hom.: 13720

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

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: rs1546550; hg19: chr12-26222745;