ENST00000621189.4:c.-995C>T

Variant names:

• chr8-144517643-G-A
• rs1315086855
• ENST00000621189.4:c.-995C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The ENST00000621189.4(RECQL4):​c.-995C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,329,810 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 Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: RECQL4 ENST00000621189.4 5_prime_UTR
• Scores: Splicing: ADA: 0.00005671
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.207
• 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: Benign. The variant received -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-144517643-G-A is Benign according to our data. Variant chr8-144517643-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 459521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.85-8C>T		splice_region intron	N/A	NP_004251.4
	RECQL4	NM_001413023.1		c.-995C>T		5_prime_UTR	Exon 1 of 19	NP_001399952.1
	RECQL4	NM_001413041.1		c.-1057C>T		5_prime_UTR	Exon 1 of 19	NP_001399970.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000621189.4	TSL:1	c.-995C>T		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.85-8C>T		splice_region intron	N/A	ENSP00000482313.2
	RECQL4	ENST00000524998.1	TSL:3	c.-146C>T		upstream_gene	N/A	ENSP00000476579.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000119 AC: 1 AN: 83918 AF XY: 0.0000208

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000319

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000827 AC: 11 AN: 1329810 Hom.: 0 Cov.: 32 AF XY: 0.00000915 AC XY: 6 AN XY: 655770

African (AFR) AF: 0.0000375 AC: 1 AN: 26672

American (AMR) AF: 0.00 AC: 0 AN: 28132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23452

East Asian (EAS) AF: 0.00 AC: 0 AN: 29724

South Asian (SAS) AF: 0.00 AC: 0 AN: 73564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00000947 AC: 10 AN: 1055942

Other (OTH) AF: 0.00 AC: 0 AN: 55196

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Baller-Gerold syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.84
PhyloP100		-0.21
PromoterAI		-0.0075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0020
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: rs1315086855; hg19: chr8-145743027;