10-44984902-G-A

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.463G>A(p.Ala155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,613,516 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: RASSF4 NM_032023.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.195

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=0.0020190477).
• BP6: Variant 10-44984902-G-A is Benign according to our data. Variant chr10-44984902-G-A is described in ClinVar as [Benign]. Clinvar id is 716157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1580/152314) while in subpopulation AFR AF= 0.0354 (1473/41580). AF 95% confidence interval is 0.0339. There are 33 homozygotes in gnomad4. There are 714 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF4	NM_032023.4	c.463G>A	p.Ala155Thr	missense_variant	6/11	ENST00000340258.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF4	ENST00000340258.10	c.463G>A	p.Ala155Thr	missense_variant	6/11	1	NM_032023.4	P1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1578 AN: 152196 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00280 AC: 703 AN: 250924 Hom.: 10 AF XY: 0.00213 AC XY: 289 AN XY: 135726

Gnomad AFR exome AF: 0.0360

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00112 AC: 1631 AN: 1461202 Hom.: 25 Cov.: 31 AF XY: 0.000985 AC XY: 716 AN XY: 726910

Gnomad4 AFR exome AF: 0.0370

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000827

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.0104 AC: 1580 AN: 152314 Hom.: 33 Cov.: 33 AF XY: 0.00959 AC XY: 714 AN XY: 74490

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00190 Hom.: 11

Bravo AF: 0.0123

ESP6500AA AF: 0.0329 AC: 145

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00337 AC: 409

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.25
Dann	Benign	0.20
DEOGEN2	Benign	0.00023	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.23	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Polyphen		0.0060	B
Vest4		0.048
MVP		0.26
MPC		0.097
ClinPred		0.000029	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.016
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs35924448; hg19: chr10-45480350; COSMIC: COSV58487620; COSMIC: COSV58487620;