rs2297492

Positions:

• chr10-44995923-T-C

Variant summary

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

The XM_047426129.1(LOC124902530):​c.273+982T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,142 control chromosomes in the GnomAD database, including 730 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 0.087 (730 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LOC124902530 XM_047426129.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

LOC124902530 (HGNC:):

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 (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124902530	XM_047426129.1	c.273+982T>C		intron_variant			XP_047282085.1
		n.44995923T>C		intergenic_region
ZNF22-AS1	NR_126421.2	n.512-1717A>G		intron_variant
RASSF4	NM_032023.4	c.*2594T>C		downstream_gene_variant		ENST00000340258.10	NP_114412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASSF4	ENST00000340258.10	c.*2594T>C		downstream_gene_variant		1	NM_032023.4	ENSP00000339692.4

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13254 AN: 152024 Hom.: 731 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.0661

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.101

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0871 AC: 13252 AN: 152142 Hom.: 730 Cov.: 32 AF XY: 0.0892 AC XY: 6634 AN XY: 74358

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0987

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.0995

Alfa AF: 0.101 Hom.: 1227

Bravo AF: 0.0848

Asia WGS AF: 0.153 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.1
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2297492; hg19: chr10-45491371;