rs7969932

Variant names:

• chr12-64528407-C-T
• rs7969932
• ENST00000637125.1:c.170-13174C>T

Variant summary

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

The ENST00000637125.1(RASSF3):​c.170-13174C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,042 control chromosomes in the GnomAD database, including 24,990 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 0.57 (24990 hom., cov: 33)
• Consequence: RASSF3 ENST00000637125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 5 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]

ENSG00000256199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369803	NR_188079.1	n.1153+4541G>A		intron_variant	Intron 3 of 3
RASSF3	XM_047428711.1	c.125-13174C>T		intron_variant	Intron 1 of 5		XP_047284667.1
RASSF3	XM_047428712.1	c.278-13174C>T		intron_variant	Intron 1 of 3		XP_047284668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASSF3	ENST00000637125.1	c.170-13174C>T		intron_variant	Intron 1 of 5	5		ENSP00000490100.1
ENSG00000256199	ENST00000541885.1	n.307+4925G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86067 AN: 151926 Hom.: 24984 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.566 AC: 86118 AN: 152042 Hom.: 24990 Cov.: 33 AF XY: 0.569 AC XY: 42302 AN XY: 74320

African (AFR) AF: 0.520 AC: 21547 AN: 41440

American (AMR) AF: 0.617 AC: 9430 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1747 AN: 3472

East Asian (EAS) AF: 0.965 AC: 5005 AN: 5184

South Asian (SAS) AF: 0.669 AC: 3225 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5743 AN: 10558

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37589 AN: 67968

Other (OTH) AF: 0.571 AC: 1207 AN: 2112

Alfa AF: 0.565 Hom.: 16775

Bravo AF: 0.570

Asia WGS AF: 0.753 AC: 2616 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs7969932; hg19: chr12-64922187;