rs1554904702

Variant names:

• chr8-144517436-G-A
• rs1554904702
• ENST00000621189.4:c.-881C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144517436-G-A
• chr8-144517436-G-C
• chr8-144517436-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_001413023.1(RECQL4):​c.-881C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,688 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: not found (cov: 35)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RECQL4 NM_001413023.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.0490
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07558143).
• BP6: Variant 8-144517436-G-A is Benign according to our data. Variant chr8-144517436-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 529027.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413023.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.191C>T	p.Ser64Leu	missense	Exon 3 of 21	NP_004251.4
	RECQL4	NM_001413023.1		c.-881C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	NP_001399952.1
	RECQL4	NM_001413041.1		c.-943C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 19	NP_001399970.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000621189.4	TSL:1	c.-881C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 20	ENSP00000483145.1
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.191C>T	p.Ser64Leu	missense	Exon 3 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.-881C>T		5_prime_UTR	Exon 2 of 20	ENSP00000483145.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1433688 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 711306

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 42314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 38894

South Asian (SAS) AF: 0.00 AC: 0 AN: 83426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4814

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103258

Other (OTH) AF: 0.0000337 AC: 2 AN: 59348

GnomAD4 genome Cov.: 35

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Baller-Gerold syndrome (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.8
DANN	Benign	0.82
DEOGEN2	Benign	0.052	T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.076	T
PhyloP100		0.049
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.11
MVP		0.71
GERP RS		0.61
PromoterAI		-0.012	Neutral
Varity_R		0.055
gMVP		0.18
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1554904702; hg19: chr8-145742820;