rs3814568

Positions:

• chr10-44991127-G-A

Variant summary

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

The NM_032023.4(RASSF4):​c.807+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,527,448 control chromosomes in the GnomAD database, including 2,845 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 0.041 (208 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2637 hom.)
• Consequence: RASSF4 NM_032023.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

RASSF4 (HGNC:20793): (Ras association domain family member 4) The function of this gene has not yet been determined but may involve a role in tumor suppression. Alternative splicing of this gene results in several transcript variants; however, most of the variants have not been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF4	NM_032023.4	c.807+58G>A		intron_variant		ENST00000340258.10	NP_114412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF4	ENST00000340258.10	c.807+58G>A		intron_variant		1	NM_032023.4	ENSP00000339692	P1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6292 AN: 152094 Hom.: 210 Cov.: 33

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0441

GnomAD3 exomes AF: 0.0632 AC: 12892 AN: 203962 Hom.: 687 AF XY: 0.0680 AC XY: 7592 AN XY: 111722

Gnomad AFR exome AF: 0.00924

Gnomad AMR exome AF: 0.0288

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.163

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.0402

Gnomad NFE exome AF: 0.0445

Gnomad OTH exome AF: 0.0579

GnomAD4 exome AF: 0.0512 AC: 70413 AN: 1375236 Hom.: 2637 Cov.: 24 AF XY: 0.0540 AC XY: 36655 AN XY: 679102

Gnomad4 AFR exome AF: 0.00680

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.0435

Gnomad4 OTH exome AF: 0.0544

GnomAD4 genome AF: 0.0413 AC: 6284 AN: 152212 Hom.: 208 Cov.: 33 AF XY: 0.0441 AC XY: 3279 AN XY: 74396

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0403 Hom.: 47

Bravo AF: 0.0376

Asia WGS AF: 0.141 AC: 488 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	0.30
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3814568; hg19: chr10-45486575; COSMIC: COSV58489705; COSMIC: COSV58489705;