12-64620009-G-C

Variant names:

• chr12-64620009-G-C
• rs12311754
• NM_178169.4:c.111+9266G>C

Variant summary

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

The NM_178169.4(RASSF3):​c.111+9266G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.40 (2703 hom., cov: 3)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF3	NM_178169.4	c.111+9266G>C		intron_variant	Intron 1 of 4	ENST00000542104.6	NP_835463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF3	ENST00000542104.6	c.111+9266G>C		intron_variant	Intron 1 of 4	1	NM_178169.4	ENSP00000443021.1
RASSF3	ENST00000637125.1	c.295-64778G>C		intron_variant	Intron 2 of 5	5		ENSP00000490100.1
RASSF3	ENST00000283172.9	n.111+9266G>C		intron_variant	Intron 1 of 3	2		ENSP00000283172.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 26441 AN: 66038 Hom.: 2695 Cov.: 3

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.401 AC: 26471 AN: 66086 Hom.: 2703 Cov.: 3 AF XY: 0.397 AC XY: 12852 AN XY: 32398

African (AFR) AF: 0.475 AC: 9517 AN: 20054

American (AMR) AF: 0.239 AC: 1477 AN: 6188

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 409 AN: 1252

East Asian (EAS) AF: 0.198 AC: 413 AN: 2090

South Asian (SAS) AF: 0.486 AC: 1145 AN: 2354

European-Finnish (FIN) AF: 0.398 AC: 1713 AN: 4302

Middle Eastern (MID) AF: 0.311 AC: 28 AN: 90

European-Non Finnish (NFE) AF: 0.397 AC: 11293 AN: 28430

Other (OTH) AF: 0.347 AC: 318 AN: 916

Alfa AF: 0.178 Hom.: 295

Asia WGS AF: 0.185 AC: 626 AN: 3364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.41
PhyloP100		-1.1
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: rs12311754; hg19: chr12-65013789; COSMIC: COSV51688139; COSMIC: COSV51688139;