rs870957

Variant names:

• chr10-44982644-A-G
• rs870957
• NM_032023.4:c.262A>G

Variant summary

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

The NM_032023.4(RASSF4):​c.262A>G​(p.Arg88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,882 control chromosomes in the GnomAD database, including 31,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4361 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27205 hom.)
• Consequence: RASSF4 NM_032023.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 34 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047510862).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032023.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF4	NM_032023.4	MANE Select	c.262A>G	p.Arg88Gly	missense	Exon 4 of 11	NP_114412.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF4	ENST00000340258.10	TSL:1 MANE Select	c.262A>G	p.Arg88Gly	missense	Exon 4 of 11	ENSP00000339692.4	Q9H2L5-1
	RASSF4	ENST00000489171.5	TSL:1	n.2268A>G		non_coding_transcript_exon	Exon 3 of 10
	RASSF4	ENST00000952763.1		c.376A>G	p.Arg126Gly	missense	Exon 5 of 12	ENSP00000622822.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34531 AN: 152018 Hom.: 4349 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.204

GnomAD2 exomes AF: 0.198 AC: 49452 AN: 249644 AF XY: 0.202

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.0995

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.317

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.187 AC: 272848 AN: 1460746 Hom.: 27205 Cov.: 33 AF XY: 0.189 AC XY: 137685 AN XY: 726654

African (AFR) AF: 0.344 AC: 11508 AN: 33430

American (AMR) AF: 0.104 AC: 4643 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4130 AN: 26058

East Asian (EAS) AF: 0.316 AC: 12526 AN: 39668

South Asian (SAS) AF: 0.283 AC: 24372 AN: 86156

European-Finnish (FIN) AF: 0.166 AC: 8846 AN: 53396

Middle Eastern (MID) AF: 0.228 AC: 1304 AN: 5722

European-Non Finnish (NFE) AF: 0.174 AC: 193751 AN: 1111390

Other (OTH) AF: 0.195 AC: 11768 AN: 60330

GnomAD4 genome AF: 0.227 AC: 34564 AN: 152136 Hom.: 4361 Cov.: 33 AF XY: 0.226 AC XY: 16825 AN XY: 74372

African (AFR) AF: 0.338 AC: 14029 AN: 41498

American (AMR) AF: 0.159 AC: 2434 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.311 AC: 1607 AN: 5168

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4832

European-Finnish (FIN) AF: 0.163 AC: 1730 AN: 10602

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12148 AN: 67952

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.193 Hom.: 11295

Bravo AF: 0.228

TwinsUK AF: 0.174 AC: 645

ALSPAC AF: 0.180 AC: 694

ESP6500AA AF: 0.337 AC: 1484

ESP6500EA AF: 0.174 AC: 1499

ExAC AF: 0.204 AC: 24751

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.44
DEOGEN2	Benign	0.00029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.11
Sift	Benign	0.41	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.13
ClinPred		0.0017	T
GERP RS		1.4
Varity_R		0.042
gMVP		0.25
Mutation Taster		=98/2	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: rs870957; hg19: chr10-45478092; COSMIC: COSV53573376; COSMIC: COSV53573376;