4-37638458-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001085400.2(RELL1):c.432T>C(p.Tyr144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,612,782 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (72 hom.)
• Consequence: RELL1 NM_001085400.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0980

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-37638458-A-G is Benign according to our data. Variant chr4-37638458-A-G is described in ClinVar as [Benign]. Clinvar id is 780459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.098 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RELL1	NM_001085400.2	c.432T>C	p.Tyr144=	synonymous_variant	4/7	ENST00000454158.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RELL1	ENST00000454158.7	c.432T>C	p.Tyr144=	synonymous_variant	4/7	5	NM_001085400.2	P1
RELL1	ENST00000314117.8	c.432T>C	p.Tyr144=	synonymous_variant	4/7	1		P1
RELL1	ENST00000512114.1	c.495T>C	p.Tyr165=	synonymous_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2646 AN: 152246 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.00437 AC: 1087 AN: 248844 Hom.: 35 AF XY: 0.00341 AC XY: 460 AN XY: 135014

Gnomad AFR exome AF: 0.0633

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000986

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000796

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00174 AC: 2548 AN: 1460418 Hom.: 72 Cov.: 29 AF XY: 0.00157 AC XY: 1142 AN XY: 726550

Gnomad4 AFR exome AF: 0.0630

Gnomad4 AMR exome AF: 0.00274

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000684

Gnomad4 OTH exome AF: 0.00343

GnomAD4 genome AF: 0.0174 AC: 2648 AN: 152364 Hom.: 87 Cov.: 32 AF XY: 0.0164 AC XY: 1225 AN XY: 74516

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.00568

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00523 Hom.: 17

Bravo AF: 0.0199

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

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

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.35
Dann	Benign	0.43

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: rs6838115; hg19: chr4-37640080;