rs882845

Positions:

• chr10-44971999-T-A
• chr10-44971999-T-G

Variant summary

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

The NM_032023.4(RASSF4):​c.138+151T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 602,498 control chromosomes in the GnomAD database, including 103,039 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 0.51 (21999 hom., cov: 32)
  • Exomes 𝑓: 0.59 (81040 hom.)
• Consequence: RASSF4 NM_032023.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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]

DEPP1 (HGNC:23355): (DEPP autophagy regulator 1) The expression of this gene is induced by fasting as well as by progesterone. The protein encoded by this gene contains a t-synaptosome-associated protein receptor (SNARE) coiled-coil homology domain and a peroxisomal targeting signal. Production of the encoded protein leads to phosphorylation and activation of the transcription factor ELK1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASSF4	NM_032023.4	c.138+151T>A		intron_variant		ENST00000340258.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASSF4	ENST00000340258.10	c.138+151T>A		intron_variant		1	NM_032023.4	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77167 AN: 151930 Hom.: 21988 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.589 AC: 265439 AN: 450448 Hom.: 81040 AF XY: 0.585 AC XY: 138325 AN XY: 236566

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.637

Gnomad4 OTH exome AF: 0.579

GnomAD4 genome AF: 0.508 AC: 77203 AN: 152050 Hom.: 21999 Cov.: 32 AF XY: 0.512 AC XY: 38068 AN XY: 74304

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.545

Alfa AF: 0.444 Hom.: 1412

Bravo AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.87

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: rs882845; hg19: chr10-45467447;