10-44984028-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032023.4(RASSF4):c.288G>T(p.Glu96Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,598,326 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (45 hom.)
• Consequence: RASSF4 NM_032023.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.417

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017531216).
• BP6: Variant 10-44984028-G-T is Benign according to our data. Variant chr10-44984028-G-T is described in ClinVar as [Benign]. Clinvar id is 780862.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0149 (2272/152324) while in subpopulation AFR AF= 0.0499 (2076/41564). AF 95% confidence interval is 0.0482. There are 64 homozygotes in gnomad4. There are 1034 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF4	NM_032023.4	c.288G>T	p.Glu96Asp	missense_variant	5/11	ENST00000340258.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF4	ENST00000340258.10	c.288G>T	p.Glu96Asp	missense_variant	5/11	1	NM_032023.4	P1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2262 AN: 152206 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00371 AC: 834 AN: 224536 Hom.: 15 AF XY: 0.00291 AC XY: 352 AN XY: 120978

Gnomad AFR exome AF: 0.0451

Gnomad AMR exome AF: 0.00392

Gnomad ASJ exome AF: 0.00403

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000739

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000350

Gnomad OTH exome AF: 0.00284

GnomAD4 exome AF: 0.00174 AC: 2516 AN: 1446002 Hom.: 45 Cov.: 31 AF XY: 0.00159 AC XY: 1141 AN XY: 717646

Gnomad4 AFR exome AF: 0.0514

Gnomad4 AMR exome AF: 0.00422

Gnomad4 ASJ exome AF: 0.00438

Gnomad4 EAS exome AF: 0.0000512

Gnomad4 SAS exome AF: 0.000156

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00450

GnomAD4 genome AF: 0.0149 AC: 2272 AN: 152324 Hom.: 64 Cov.: 33 AF XY: 0.0139 AC XY: 1034 AN XY: 74486

Gnomad4 AFR AF: 0.0499

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00768 Hom.: 18

Bravo AF: 0.0176

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0493 AC: 217

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.00424 AC: 514

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	5.2
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0021	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.093
Sift	Benign	0.35	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.0020	B;.
Vest4		0.19
MutPred		0.15		Loss of helix (P = 0.0444);.;
MVP		0.34
MPC		0.090
ClinPred		0.0090	T
GERP RS		0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs79857424; hg19: chr10-45479476;