Genetic Variant RELL1:c.89-33T>C (chr4-37649533-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

8 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085400.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELL1	NM_001085400.2	MANE Select	c.89-33T>C		intron	N/A	NP_001078869.1
	RELL1	NM_001085399.2		c.89-33T>C		intron	N/A	NP_001078868.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RELL1	ENST00000454158.7	TSL:5 MANE Select	c.89-33T>C	intron	N/A	ENSP00000398778.2
RELL1	ENST00000314117.8	TSL:1	c.89-33T>C	intron	N/A	ENSP00000313385.4
RELL1	ENST00000512114.1	TSL:3	c.152-33T>C	intron	N/A	ENSP00000424031.1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47884

AN:

152062

Hom.:

7720

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.325

AC:

79679

AN:

245468

AF XY:

0.326

show subpopulations

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 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.:

AF XY:

0.355

AC XY:

252238

AN XY:

710406

show subpopulations

African (AFR)

AF:

0.242

AC:

7928

AN:

32704

American (AMR)

AF:

0.235

AC:

10420

AN:

44386

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

10517

AN:

25640

East Asian (EAS)

AF:

0.298

AC:

11766

AN:

39528

South Asian (SAS)

AF:

0.278

AC:

23621

AN:

85120

European-Finnish (FIN)

AF:

0.294

AC:

15660

AN:

53232

Middle Eastern (MID)

AF:

0.376

AC:

1642

AN:

4364

European-Non Finnish (NFE)

AF:

0.377

AC:

406965

AN:

1080876

Other (OTH)

AF:

0.347

AC:

20486

AN:

58974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

16739

33478

50218

66957

83696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12608

25216

37824

50432

63040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.315

AC:

47905

AN:

152180

Hom.:

7720

Cov.:

AF XY:

0.308

AC XY:

22884

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.246

AC:

10221

AN:

41514

American (AMR)

AF:

0.272

AC:

4153

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1466

AN:

3472

East Asian (EAS)

AF:

0.284

AC:

1469

AN:

5174

South Asian (SAS)

AF:

0.282

AC:

1361

AN:

4826

European-Finnish (FIN)

AF:

0.274

AC:

2906

AN:

10588

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25175

AN:

68002

Other (OTH)

AF:

0.324

AC:

682

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1768

3535

5303

7070

8838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.337

Hom.:

9310

Bravo

AF:

0.315

Asia WGS

AF:

0.261

AC:

906

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.052

(source)

DANN

Benign

0.26

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over