chr12-64526196-C-A

Position:

• chr12-64526196-C-A

Variant summary

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

The ENST00000541885.1(ENSG00000256199):​n.307+7136G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,016 control chromosomes in the GnomAD database, including 16,193 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 (16193 hom., cov: 32)
• Consequence: ENST00000541885.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

Genes affected

(HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105369803	XR_002957417.1	n.534+7136G>T		intron_variant, non_coding_transcript_variant
RASSF3	XM_047428711.1	c.125-15385C>A		intron_variant			XP_047284667.1
RASSF3	XM_047428712.1	c.278-15385C>A		intron_variant			XP_047284668.1
LOC105369803	XR_945026.3	n.793+7136G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000541885.1	n.307+7136G>T		intron_variant, non_coding_transcript_variant		3
RASSF3	ENST00000637125.1	c.170-15385C>A		intron_variant		5		ENSP00000490100	A2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67244 AN: 151898 Hom.: 16192 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.442 AC: 67261 AN: 152016 Hom.: 16193 Cov.: 32 AF XY: 0.455 AC XY: 33800 AN XY: 74300

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.464

Alfa AF: 0.463 Hom.: 20113

Bravo AF: 0.432

Asia WGS AF: 0.662 AC: 2299 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.60
DANN	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2141765; hg19: chr12-64919976;