dbSNP rs765509960: RAD21L1:p.Ile125Val (chr20-1234089-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001384358.1(RAD21L1):c.-267A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000137 in 1,472,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RAD21L1
NM_001384358.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

0 publications found

Variant links:

Genes affected

RAD21L1 (HGNC:16271): (RAD21 cohesin complex component like 1) Predicted to enable chromatin binding activity. Predicted to be involved in mitotic sister chromatid cohesion; replication-born double-strand break repair via sister chromatid exchange; and synaptonemal complex assembly. Predicted to act upstream of or within several processes, including double-strand break repair via homologous recombination; homologous chromosome segregation; and seminiferous tubule development. Predicted to be located in lateral element. Predicted to be part of nuclear meiotic cohesin complex and nuclear mitotic cohesin complex. Predicted to be active in synaptonemal complex. [provided by Alliance of Genome Resources, Apr 2022]

RAD21L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.074166566).

BS2

High AC in GnomAd4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384358.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD21L1	NM_001384355.1	MANE Select	c.373A>G	p.Ile125Val	missense	Exon 5 of 14	NP_001371284.1	A0A804HJ87
RAD21L1	NM_001384358.1		c.-267A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001371287.1
RAD21L1	NM_001136566.3		c.373A>G	p.Ile125Val	missense	Exon 5 of 14	NP_001130038.2	Q9H4I0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD21L1	ENST00000683101.1	MANE Select	c.373A>G	p.Ile125Val	missense	Exon 5 of 14	ENSP00000507397.1	A0A804HJ87
RAD21L1	ENST00000409241.5	TSL:1	c.373A>G	p.Ile125Val	missense	Exon 5 of 14	ENSP00000386414.1	Q9H4I0-1
RAD21L1	ENST00000402452.5	TSL:5	c.373A>G	p.Ile125Val	missense	Exon 5 of 14	ENSP00000385925.1	Q9H4I0-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000110

AC:

AN:

154060

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000420

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000138

AC:

182

AN:

1320748

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

655112

show subpopulations

African (AFR)

AF:

0.0000668

AC:

AN:

29930

American (AMR)

AF:

0.0000573

AC:

AN:

34934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24566

East Asian (EAS)

AF:

0.00

AC:

AN:

35216

South Asian (SAS)

AF:

0.0000132

AC:

AN:

75922

European-Finnish (FIN)

AF:

0.0000610

AC:

AN:

49198

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.000167

AC:

169

AN:

1010174

Other (OTH)

AF:

0.0000724

AC:

AN:

55268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000131

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000214

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000805

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.086

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.62

M_CAP

Benign

0.0038

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

4.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.53

REVEL

Benign

0.058

Sift

Benign

0.18

Sift4G

Benign

0.079

Polyphen

0.0060

Vest4

0.13

MVP

0.076

ClinPred

0.088

GERP RS

1.2

Varity_R

0.042

gMVP

0.12

Mutation Taster

=91/9

polymorphism

(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