rs2292298

Positions:

• chr4-37649533-A-G

Variant summary

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

The NM_001085400.2(RELL1):​c.89-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,577,004 control chromosomes in the GnomAD database, including 100,447 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 0.31 (7720 hom., cov: 33)
  • Exomes 𝑓: 0.36 (92727 hom.)
• Consequence: RELL1 NM_001085400.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

Genes affected

RELL1 (HGNC:27379): (RELT like 1) Involved in positive regulation of p38MAPK cascade. Located in microtubule cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RELL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELL1	NM_001085400.2	c.89-33T>C		intron_variant		ENST00000454158.7	NP_001078869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELL1	ENST00000454158.7	c.89-33T>C		intron_variant		5	NM_001085400.2	ENSP00000398778.2
RELL1	ENST00000314117.8	c.89-33T>C		intron_variant		1		ENSP00000313385.4
RELL1	ENST00000512114.1	c.152-33T>C		intron_variant		3		ENSP00000424031.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47884 AN: 152062 Hom.: 7720 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.326

GnomAD3 exomes AF: 0.325 AC: 79679 AN: 245468 Hom.: 13465 AF XY: 0.326 AC XY: 43468 AN XY: 133238

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.412

Gnomad EAS exome AF: 0.311

Gnomad SAS exome AF: 0.280

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.357 AC: 509005 AN: 1424824 Hom.: 92727 Cov.: 24 AF XY: 0.355 AC XY: 252238 AN XY: 710406

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.315 AC: 47905 AN: 152180 Hom.: 7720 Cov.: 33 AF XY: 0.308 AC XY: 22884 AN XY: 74396

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.324

Alfa AF: 0.353 Hom.: 5641

Bravo AF: 0.315

Asia WGS AF: 0.261 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.052
DANN	Benign	0.26

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: rs2292298; hg19: chr4-37651155; COSMIC: COSV58452015;