rs12142

Positions:

• chr4-37610904-G-A
• chr4-37610904-G-T

Variant summary

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

The NM_001085400.2(RELL1):​c.*2442C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,076 control chromosomes in the GnomAD database, including 8,189 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 0.29 (8189 hom., cov: 33)
• Consequence: RELL1 NM_001085400.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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]

C4orf19 (HGNC:25618): (chromosome 4 open reading frame 19) Located in cell junction and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELL1	NM_001085400.2	c.*2442C>T		3_prime_UTR_variant	7/7	ENST00000454158.7	NP_001078869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELL1	ENST00000454158.7	c.*2442C>T		3_prime_UTR_variant	7/7	5	NM_001085400.2	ENSP00000398778	P1
RELL1	ENST00000314117.8	c.*4-19687C>T		intron_variant		1		ENSP00000313385	P1
C4orf19	ENST00000508175.5	c.33-11921G>A		intron_variant		3		ENSP00000421537

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44372 AN: 151958 Hom.: 8191 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44371 AN: 152076 Hom.: 8189 Cov.: 33 AF XY: 0.293 AC XY: 21753 AN XY: 74312

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.288

Alfa AF: 0.365 Hom.: 9734

Bravo AF: 0.262

Asia WGS AF: 0.164 AC: 570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.73

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: rs12142; hg19: chr4-37612526;