20-4800552-T-C

Position:

• chr20-4800552-T-C

Variant summary

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

The NM_014737.3(RASSF2):​c.59+420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,958 control chromosomes in the GnomAD database, including 31,803 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 0.64 (31803 hom., cov: 31)
• Consequence: RASSF2 NM_014737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

Genes affected

RASSF2 (HGNC:9883): (Ras association domain family member 2) This gene encodes a protein that contains a Ras association domain. Similar to its cattle and sheep counterparts, this gene is located near the prion gene. Two alternatively spliced transcripts encoding the same isoform have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF2	NM_014737.3	c.59+420A>G		intron_variant		ENST00000379400.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF2	ENST00000379400.8	c.59+420A>G		intron_variant		1	NM_014737.3	P1
RASSF2	ENST00000379376.2	c.59+420A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97411 AN: 151840 Hom.: 31768 Cov.: 31

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.642 AC: 97497 AN: 151958 Hom.: 31803 Cov.: 31 AF XY: 0.637 AC XY: 47325 AN XY: 74282

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.639

Alfa AF: 0.600 Hom.: 14595

Bravo AF: 0.659

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.47

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: rs1535382; hg19: chr20-4781198;