rs199654783

Positions:

• chr8-144514220-T-C
• chr8-144514220-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_004260.4(RECQL4):​c.1847A>G​(p.Asn616Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000617 in 1,612,112 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00061 (2 hom.)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.70

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09313479).
• BP6: Variant 8-144514220-T-C is Benign according to our data. Variant chr8-144514220-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 239710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1847A>G	p.Asn616Ser	missense_variant	11/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1847A>G	p.Asn616Ser	missense_variant	11/21	1	NM_004260.4	ENSP00000482313	P1
RECQL4	ENST00000621189.4	c.776A>G	p.Asn259Ser	missense_variant	10/20	1		ENSP00000483145
RECQL4	ENST00000534626.6	c.218A>G	p.Asn73Ser	missense_variant	2/8	5		ENSP00000477457
RECQL4	ENST00000532846.2	c.704A>G	p.Asn235Ser	missense_variant	7/9	5		ENSP00000476551

Frequencies

GnomAD3 genomes AF: 0.000678 AC: 103 AN: 151878 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000648

Gnomad OTH AF: 0.000961

GnomAD3 exomes AF: 0.000533 AC: 131 AN: 245662 Hom.: 1 AF XY: 0.000441 AC XY: 59 AN XY: 133850

Gnomad AFR exome AF: 0.0000656

Gnomad AMR exome AF: 0.00186

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000500

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.000610 AC: 891 AN: 1460116 Hom.: 2 Cov.: 36 AF XY: 0.000606 AC XY: 440 AN XY: 726342

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.00210

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000577

Gnomad4 NFE exome AF: 0.000676

Gnomad4 OTH exome AF: 0.000646

GnomAD4 genome AF: 0.000678 AC: 103 AN: 151996 Hom.: 0 Cov.: 34 AF XY: 0.000673 AC XY: 50 AN XY: 74298

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000648

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.000446 Hom.: 0

Bravo AF: 0.00100

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000476 AC: 4

ExAC AF: 0.000514 AC: 62

EpiCase AF: 0.000273

EpiControl AF: 0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2021	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30995915) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Baller-Gerold syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Jan 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.89
DEOGEN2	Benign	0.11	T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.093	T;T
PrimateAI	Uncertain	0.51	T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.94	.;P
Vest4		0.72
MVP		0.77
GERP RS		5.0
Varity_R		0.23
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs199654783; hg19: chr8-145739604; COSMIC: COSV105873954; COSMIC: COSV105873954;