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1-40202572-A-G

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Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_012421.4(RLF):ā€‹c.768A>Gā€‹(p.Thr256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,559,008 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.0051 ( 6 hom., cov: 32)
Exomes š‘“: 0.00052 ( 6 hom. )

Consequence

RLF
NM_012421.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.198
Variant links:
Genes affected
RLF (HGNC:10025): (RLF zinc finger) Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within histone H3-K4 monomethylation and regulation of DNA methylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-40202572-A-G is Benign according to our data. Variant chr1-40202572-A-G is described in ClinVar as [Benign]. Clinvar id is 726801.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.198 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (773/152330) while in subpopulation AFR AF= 0.0173 (718/41574). AF 95% confidence interval is 0.0162. There are 6 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd4 at 773 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RLFNM_012421.4 linkuse as main transcriptc.768A>G p.Thr256= synonymous_variant 5/8 ENST00000372771.5
RLFXM_047427055.1 linkuse as main transcriptc.120A>G p.Thr40= synonymous_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RLFENST00000372771.5 linkuse as main transcriptc.768A>G p.Thr256= synonymous_variant 5/81 NM_012421.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00505
AC:
768
AN:
152212
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0172
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00288
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00144
AC:
288
AN:
199884
Hom.:
3
AF XY:
0.00103
AC XY:
113
AN XY:
109952
show subpopulations
Gnomad AFR exome
AF:
0.0185
Gnomad AMR exome
AF:
0.00140
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000460
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000604
Gnomad OTH exome
AF:
0.000650
GnomAD4 exome
AF:
0.000525
AC:
738
AN:
1406678
Hom.:
6
Cov.:
29
AF XY:
0.000472
AC XY:
330
AN XY:
699186
show subpopulations
Gnomad4 AFR exome
AF:
0.0192
Gnomad4 AMR exome
AF:
0.00138
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000669
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000465
Gnomad4 OTH exome
AF:
0.00112
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00507
AC:
773
AN:
152330
Hom.:
6
Cov.:
32
AF XY:
0.00520
AC XY:
387
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0173
Gnomad4 AMR
AF:
0.00288
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00332
Alfa
AF:
0.00244
Hom.:
1
Bravo
AF:
0.00609
Asia WGS
AF:
0.00144
AC:
5
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
11
DANN
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs112377652; hg19: chr1-40668244; API