12-64622520-A-G

Variant names:

• chr12-64622520-A-G
• rs17120527
• NM_178169.4:c.111+11777A>G

Variant summary

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

The NM_178169.4(RASSF3):​c.111+11777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 530,676 control chromosomes in the GnomAD database, including 890 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 0.053 (725 hom., cov: 30)
  • Exomes 𝑓: 0.0066 (165 hom.)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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]

MIR548C (HGNC:32800): (microRNA 548c) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR548Z (HGNC:38929): (microRNA 548z) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF3	NM_178169.4	c.111+11777A>G		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+11777A>G		intron_variant	Intron 1 of 4	1	NM_178169.4	ENSP00000443021.1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7986 AN: 151900 Hom.: 723 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0141 AC: 3483 AN: 246442 Hom.: 293 AF XY: 0.0100 AC XY: 1338 AN XY: 133692

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.00974

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.000918

Gnomad OTH exome AF: 0.00776

GnomAD4 exome AF: 0.00664 AC: 2516 AN: 378658 Hom.: 165 Cov.: 0 AF XY: 0.00512 AC XY: 1105 AN XY: 215824

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000391

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.000590

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0526 AC: 7996 AN: 152018 Hom.: 725 Cov.: 30 AF XY: 0.0502 AC XY: 3730 AN XY: 74356

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000751

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0143 Hom.: 210

Bravo AF: 0.0611

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
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: rs17120527; hg19: chr12-65016300;