Variant rs200516441 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000617875.6(RECQL4):c.275C>T(p.Ser92Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,612,184 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S92P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0081 ( 14 hom., cov: 34)

Exomes 𝑓: 0.00086 ( 21 hom. )

Consequence

RECQL4
ENST00000617875.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.0530

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003534019).

BP6

Variant 8-144517129-G-A is Benign according to our data. Variant chr8-144517129-G-A is described in ClinVar as [Benign]. Clinvar id is 197231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00814 (1240/152376) while in subpopulation AFR AF= 0.0284 (1182/41592). AF 95% confidence interval is 0.0271. There are 14 homozygotes in gnomad4. There are 589 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.275C>T	p.Ser92Phe	missense_variant	4/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 linkuse as main transcript	c.275C>T	p.Ser92Phe	missense_variant	4/21	1	NM_004260.4	ENSP00000482313	P1

Frequencies

GnomAD3 genomes

AF:

0.00814

AC:

1240

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00191

AC:

468

AN:

245212

Hom.:

AF XY:

0.00145

AC XY:

195

AN XY:

134150

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.000670

GnomAD4 exome

AF:

0.000859

AC:

1254

AN:

1459808

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

536

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00814

AC:

1240

AN:

152376

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0284

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00947

ExAC

AF:

0.00216

AC:

260

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 09, 2014	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.77

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0035

PrimateAI

Benign

0.34

Sift4G

Benign

0.080

Vest4

0.22

MVP

0.34

GERP RS

3.1

Varity_R

0.044

gMVP

0.17

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over