chr12-26060787-C-T

Position:

• chr12-26060787-C-T

Variant summary

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

The NM_001394098.1(RASSF8):​c.104-3711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,108 control chromosomes in the GnomAD database, including 908 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 0.11 (908 hom., cov: 33)
• Consequence: RASSF8 NM_001394098.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF8	NM_001394098.1	c.104-3711C>T		intron_variant		ENST00000689635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF8	ENST00000689635.1	c.104-3711C>T		intron_variant			NM_001394098.1	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16064 AN: 151990 Hom.: 905 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.0922

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

GnomAD4 genome AF: 0.106 AC: 16083 AN: 152108 Hom.: 908 Cov.: 33 AF XY: 0.104 AC XY: 7730 AN XY: 74380

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0650

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0943

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.0923 Hom.: 980

Bravo AF: 0.105

Asia WGS AF: 0.157 AC: 542 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.32
DANN	Benign	0.87

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: rs956627; hg19: chr12-26213720;