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rs199885535

chr8-144511485-G-Achr8-144511485-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_004260.4(RECQL4):c.3573C>T(p.Ser1191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,612,618 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.498
Variant links:
Genes affected
RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-144511485-G-A is Benign according to our data. Variant chr8-144511485-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 239767.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
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=0.498 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RECQL4NM_004260.4 linkuse as main transcriptc.3573C>T p.Ser1191= synonymous_variant 21/21 ENST00000617875.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RECQL4ENST00000617875.6 linkuse as main transcriptc.3573C>T p.Ser1191= synonymous_variant 21/211 NM_004260.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000145
AC:
22
AN:
152228
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000170
AC:
42
AN:
247758
Hom.:
0
AF XY:
0.000185
AC XY:
25
AN XY:
134996
show subpopulations
Gnomad AFR exome
AF:
0.0000653
Gnomad AMR exome
AF:
0.0000870
Gnomad ASJ exome
AF:
0.00321
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.000498
GnomAD4 exome
AF:
0.000110
AC:
160
AN:
1460272
Hom.:
0
Cov.:
33
AF XY:
0.000123
AC XY:
89
AN XY:
726402
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00360
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000144
AC:
22
AN:
152346
Hom.:
0
Cov.:
34
AF XY:
0.0000805
AC XY:
6
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000247
Hom.:
0
Bravo
AF:
0.000185
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submittercurationSema4, Sema4Aug 19, 2021- -
Baller-Gerold syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
3.9
Dann
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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.

Other links and lift over

dbSNP: rs199885535; hg19: chr8-145736868; COSMIC: COSV56740238; COSMIC: COSV56740238; API