Variant 4-37686239-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001085400.2(RELL1):c.49T>C(p.Phe17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,580,932 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 119 hom., cov: 34)

Exomes 𝑓: 0.0020 ( 93 hom. )

Consequence

RELL1
NM_001085400.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.14

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017594099).

BP6

Variant 4-37686239-A-G is Benign according to our data. Variant chr4-37686239-A-G is described in ClinVar as [Benign]. Clinvar id is 709677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELL1	NM_001085400.2 linkuse as main transcript	c.49T>C	p.Phe17Leu	missense_variant	1/7	ENST00000454158.7	NP_001078869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELL1	ENST00000454158.7 linkuse as main transcript	c.49T>C	p.Phe17Leu	missense_variant	1/7	5	NM_001085400.2	ENSP00000398778	P1
RELL1	ENST00000314117.8 linkuse as main transcript	c.49T>C	p.Phe17Leu	missense_variant	1/7	1		ENSP00000313385	P1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3291

AN:

152016

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00378

AC:

747

AN:

197384

Hom.:

AF XY:

0.00293

AC XY:

325

AN XY:

111074

show subpopulations

Gnomad AFR exome

AF:

0.0730

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00122

GnomAD4 exome

AF:

0.00198

AC:

2835

AN:

1428806

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1207

AN XY:

710844

show subpopulations

Gnomad4 AFR exome

AF:

0.0775

Gnomad4 AMR exome

AF:

0.00296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000362

Gnomad4 OTH exome

AF:

0.00468

GnomAD4 genome

AF:

0.0217

AC:

3300

AN:

152126

Hom.:

119

Cov.:

AF XY:

0.0209

AC XY:

1555

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0760

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00855

Hom.:

Bravo

AF:

0.0248

ESP6500AA

AF:

0.0561

AC:

205

ESP6500EA

AF:

0.000375

AC:

ExAC

AF:

0.00534

AC:

624

Asia WGS

AF:

0.00318

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.61

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

0.98

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.049

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.052

T;T

Polyphen

0.0010

B;B

Vest4

0.25

MutPred

0.35

Loss of catalytic residue at F17 (P = 0.0077);Loss of catalytic residue at F17 (P = 0.0077);

MVP

0.043

MPC

1.3

ClinPred

0.053

GERP RS

2.4

Varity_R

0.18

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over