rs368908286

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The ENST00000617875.6(RECQL4):ā€‹c.2724T>Cā€‹(p.Leu908=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,597,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00033 ( 1 hom., cov: 34)
Exomes š‘“: 0.00015 ( 0 hom. )

Consequence

RECQL4
ENST00000617875.6 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.13
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 Benign. Variant got -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 8-144512878-A-G is Benign according to our data. Variant chr8-144512878-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 239745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512878-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2.13 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RECQL4NM_004260.4 linkuse as main transcriptc.2724T>C p.Leu908= synonymous_variant 15/21 ENST00000617875.6 NP_004251.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RECQL4ENST00000617875.6 linkuse as main transcriptc.2724T>C p.Leu908= synonymous_variant 15/211 NM_004260.4 ENSP00000482313 P1
RECQL4ENST00000621189.4 linkuse as main transcriptc.1653T>C p.Leu551= synonymous_variant 14/201 ENSP00000483145
ENST00000580385.1 linkuse as main transcriptn.271+41A>G intron_variant, non_coding_transcript_variant 3
RECQL4ENST00000534626.6 linkuse as main transcriptc.897T>C p.Leu299= synonymous_variant 6/85 ENSP00000477457

Frequencies

GnomAD3 genomes
AF:
0.000328
AC:
50
AN:
152214
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.000865
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:
0.000478
GnomAD3 exomes
AF:
0.000225
AC:
50
AN:
222164
Hom.:
0
AF XY:
0.000215
AC XY:
26
AN XY:
120860
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000632
Gnomad ASJ exome
AF:
0.00184
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000708
Gnomad OTH exome
AF:
0.00108
GnomAD4 exome
AF:
0.000154
AC:
222
AN:
1445536
Hom.:
0
Cov.:
67
AF XY:
0.000138
AC XY:
99
AN XY:
717634
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.000564
Gnomad4 ASJ exome
AF:
0.00136
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000127
Gnomad4 OTH exome
AF:
0.000301
GnomAD4 genome
AF:
0.000328
AC:
50
AN:
152332
Hom.:
1
Cov.:
34
AF XY:
0.000470
AC XY:
35
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.00248
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000335
Hom.:
0
Bravo
AF:
0.000204

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 30, 2021- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022RECQL4: BP4, BP7 -
Baller-Gerold syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 24, 2024- -
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submittercurationSema4, Sema4Nov 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.017
DANN
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs368908286; hg19: chr8-145738261; API