12-64609189-T-G

Position:

• chr12-64609189-T-G

Variant summary

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

The ENST00000637125.1(RASSF3):​c.294+67484T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,624 control chromosomes in the GnomAD database, including 15,480 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 0.44 (15480 hom., cov: 30)
• Consequence: RASSF3 ENST00000637125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

Genes affected

RASSF3 (HGNC:14271): (Ras association domain family member 3) The RAS oncogene (MIM 190020) is mutated in nearly one-third of all human cancers. Members of the RAS superfamily are plasma membrane GTP-binding proteins that modulate intracellular signal transduction pathways. A subfamily of RAS effectors, including RASSF3, share a RAS association (RA) domain.[supplied by OMIM, Jul 2003]

RASSF3-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF3	XM_047428711.1	c.249+67484T>G		intron_variant			XP_047284667.1
RASSF3	XM_047428712.1	c.402+67484T>G		intron_variant			XP_047284668.1
RASSF3-DT	NR_187549.1	n.122+156A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF3	ENST00000637125.1	c.294+67484T>G		intron_variant		5		ENSP00000490100.1
RASSF3-DT	ENST00000546135.1	n.115+156A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67293 AN: 151506 Hom.: 15456 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.444 AC: 67356 AN: 151624 Hom.: 15480 Cov.: 30 AF XY: 0.439 AC XY: 32508 AN XY: 74082

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.435

Alfa AF: 0.432 Hom.: 11540

Bravo AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6581580; hg19: chr12-65002969;