GeneBe

rs750560547

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001413019.1(RECQL4):​c.2960+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

RECQL4
NM_001413019.1 splice_region, intron

Scores

2
Splicing: ADA: 0.0008198
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

0 publications found
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]
RECQL4 Gene-Disease associations (from GenCC):
  • Baller-Gerold syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
  • Rothmund-Thomson syndrome
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • Rothmund-Thomson syndrome type 2
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
  • osteosarcoma
    Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
  • rapadilino syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413019.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RECQL4
NM_004260.4
MANE Select
c.2885+5G>C
splice_region intron
N/ANP_004251.4
RECQL4
NM_001413019.1
c.2960+5G>C
splice_region intron
N/ANP_001399948.1
RECQL4
NM_001413036.1
c.2885+5G>C
splice_region intron
N/ANP_001399965.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RECQL4
ENST00000617875.6
TSL:1 MANE Select
c.2885+5G>C
splice_region intron
N/AENSP00000482313.2
RECQL4
ENST00000621189.4
TSL:1
c.1814+5G>C
splice_region intron
N/AENSP00000483145.1
RECQL4
ENST00000971710.1
c.2792+5G>C
splice_region intron
N/AENSP00000641769.1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
68
GnomAD4 genome
Cov.:
34

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Baller-Gerold syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
9.7
DANN
Benign
0.85
PhyloP100
1.7
PromoterAI
0.027
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00082
dbscSNV1_RF
Benign
0.0020
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs750560547; hg19: chr8-145738020; API