rs747029514

Variant names:

• chr8-144513202-G-A
• rs747029514
• NM_004260.4:c.2463+16C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144513202-G-A
• chr8-144513202-G-C
• chr8-144513202-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004260.4(RECQL4):​c.2463+16C>T variant causes a 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL4 NM_004260.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 1 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

ENSG00000265393 (HGNC:):

ACMG classification

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=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2463+16C>T		intron_variant	Intron 14 of 20	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2463+16C>T		intron_variant	Intron 14 of 20	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.1392+16C>T		intron_variant	Intron 13 of 19	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.634-64C>T		intron_variant	Intron 5 of 7	5		ENSP00000477457.1
ENSG00000265393	ENST00000580385.1	n.271+365G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.23e-7 AC: 1 AN: 1383316 Hom.: 0 Cov.: 50 AF XY: 0.00000147 AC XY: 1 AN XY: 682508

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32598

American (AMR) AF: 0.00 AC: 0 AN: 41816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23490

East Asian (EAS) AF: 0.00 AC: 0 AN: 37708

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5044

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072318

Other (OTH) AF: 0.00 AC: 0 AN: 57330

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.23
DANN	Benign	0.79
PhyloP100		-1.4
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs747029514; hg19: chr8-145738585;