rs758179747

Variant names:

• chr8-144517456-G-A
• rs758179747
• NM_004260.4:c.171C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144517456-G-A
• chr8-144517456-G-C
• chr8-144517456-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_004260.4(RECQL4):​c.171C>T​(p.Gly57Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000646 in 1,594,490 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000062 (1 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.252
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 8-144517456-G-A is Benign according to our data. Variant chr8-144517456-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 414185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.252 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. 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.171C>T	p.Gly57Gly	synonymous	Exon 3 of 21	NP_004251.4
	RECQL4	NM_001413019.1		c.171C>T	p.Gly57Gly	synonymous	Exon 3 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.171C>T	p.Gly57Gly	synonymous	Exon 3 of 21	NP_001399965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.171C>T	p.Gly57Gly	synonymous	Exon 3 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.-901C>T		5_prime_UTR	Exon 2 of 20	ENSP00000483145.1
	RECQL4	ENST00000524998.1	TSL:3	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 4	ENSP00000476579.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152206 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000157 AC: 33 AN: 210614 AF XY: 0.000145

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000613

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00161

Gnomad FIN exome AF: 0.0000701

Gnomad NFE exome AF: 0.0000216

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.0000617 AC: 89 AN: 1442168 Hom.: 1 Cov.: 32 AF XY: 0.0000670 AC XY: 48 AN XY: 716490

African (AFR) AF: 0.000150 AC: 5 AN: 33246

American (AMR) AF: 0.0000690 AC: 3 AN: 43464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25864

East Asian (EAS) AF: 0.00196 AC: 77 AN: 39260

South Asian (SAS) AF: 0.00 AC: 0 AN: 84400

European-Finnish (FIN) AF: 0.0000227 AC: 1 AN: 44058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107186

Other (OTH) AF: 0.0000502 AC: 3 AN: 59740

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152322 Hom.: 0 Cov.: 35 AF XY: 0.0000806 AC XY: 6 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000102

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Baller-Gerold syndrome (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	RECQL4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.6
DANN	Benign	0.92
PhyloP100		0.25
PromoterAI		-0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	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: rs758179747; hg19: chr8-145742840;