Genetic Variant ENST00000621189.4:c.-1129G>T (chr8-144517777-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000621189.4(RECQL4):c.-1129G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000525 in 1,238,936 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

RECQL4
ENST00000621189.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: -0.131

Publications

0 publications found

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:

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

LRRC14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21920276).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	NM_004260.4	MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 1 of 21	NP_004251.4	O94761
RECQL4	NM_001413023.1		c.-1129G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001399952.1
RECQL4	NM_001413041.1		c.-1191G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001399970.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	ENST00000621189.4	TSL:1	c.-1129G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 1 of 21	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.-1129G>T		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1	A0A087X072

Frequencies

GnomAD3 genomes

AF:

0.000292

AC:

AN:

150724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000993

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000397

AC:

AN:

25200

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00340

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1088104

Hom.:

Cov.:

AF XY:

0.0000173

AC XY:

AN XY:

521510

show subpopulations

African (AFR)

AF:

0.000684

AC:

AN:

21940

American (AMR)

AF:

0.000182

AC:

AN:

10996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15136

East Asian (EAS)

AF:

0.00

AC:

AN:

23046

South Asian (SAS)

AF:

0.00

AC:

AN:

30196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2930

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919428

Other (OTH)

AF:

0.0000942

AC:

AN:

42446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000292

AC:

AN:

150832

Hom.:

Cov.:

AF XY:

0.000394

AC XY:

AN XY:

73664

show subpopulations

African (AFR)

AF:

0.000990

AC:

AN:

41408

American (AMR)

AF:

0.000198

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67496

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000302

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Baller-Gerold syndrome (1)

not provided (1)

Rothmund-Thomson syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.22

PhyloP100

-0.13

PrimateAI

Pathogenic

0.88

Sift4G

Uncertain

0.017

Polyphen

0.99

Vest4

0.26

MVP

0.63

GERP RS

1.5

PromoterAI

-0.0067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.27

gMVP

0.16

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over