chr10-44982644-A-G

Position:

• chr10-44982644-A-G

Variant summary

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

The ENST00000340258.10(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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (4361 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27205 hom.)
• Consequence: RASSF4 ENST00000340258.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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 (MetaRNN=0.0047510862).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASSF4	NM_032023.4	c.262A>G	p.Arg88Gly	missense_variant	4/11	ENST00000340258.10	NP_114412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF4	ENST00000340258.10	c.262A>G	p.Arg88Gly	missense_variant	4/11	1	NM_032023.4	ENSP00000339692	P1

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

GnomAD3 exomes AF: 0.198 AC: 49452 AN: 249644 Hom.: 5602 AF XY: 0.202 AC XY: 27262 AN XY: 135014

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 SAS exome AF: 0.287

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

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.195

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

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.202

Alfa AF: 0.191 Hom.: 7657

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 v4.3

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;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.11	T;T;T
MetaRNN	Benign	0.0048	T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.39	T;T;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

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: rs870957; hg19: chr10-45478092; COSMIC: COSV53573376; COSMIC: COSV53573376;