chr12-64621464-G-A

Variant names:

• chr12-64621464-G-A
• rs1147098
• NM_178169.4:c.111+10721G>A

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+10721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,892 control chromosomes in the GnomAD database, including 19,033 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 0.50 (19033 hom., cov: 31)
• Consequence: RASSF3 NM_178169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASSF3	NM_178169.4	c.111+10721G>A		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+10721G>A		intron_variant	Intron 1 of 4	1	NM_178169.4	ENSP00000443021.1
RASSF3	ENST00000637125.1	c.295-63323G>A		intron_variant	Intron 2 of 5	5		ENSP00000490100.1
RASSF3	ENST00000283172.9	n.111+10721G>A		intron_variant	Intron 1 of 3	2		ENSP00000283172.4

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75624 AN: 151776 Hom.: 19019 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.498 AC: 75669 AN: 151892 Hom.: 19033 Cov.: 31 AF XY: 0.491 AC XY: 36476 AN XY: 74230

African (AFR) AF: 0.502 AC: 20788 AN: 41396

American (AMR) AF: 0.485 AC: 7389 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3464

East Asian (EAS) AF: 0.254 AC: 1314 AN: 5164

South Asian (SAS) AF: 0.462 AC: 2227 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 4992 AN: 10542

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35619 AN: 67960

Other (OTH) AF: 0.487 AC: 1023 AN: 2102

Alfa AF: 0.514 Hom.: 62793

Bravo AF: 0.499

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.4
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: rs1147098; hg19: chr12-65015244;