Genetic Variant RECQL4:c.-1127C>T (chr8-144517775-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001413023.1(RECQL4):c.-1127C>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 0.0000499 in 1,262,060 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: 𝑓 0.00025 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

RECQL4
NM_001413023.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.309

Publications

1 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 8-144517775-G-A is Benign according to our data. Variant chr8-144517775-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 239692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413023.1. 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.10C>T	p.Leu4Leu	synonymous	Exon 1 of 21	NP_004251.4	O94761
RECQL4	NM_001413023.1		c.-1127C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001399952.1
RECQL4	NM_001413041.1		c.-1189C>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.-1127C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.10C>T	p.Leu4Leu	synonymous	Exon 1 of 21	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.-1127C>T		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1	A0A087X072

Frequencies

GnomAD3 genomes

AF:

0.000245

AC:

AN:

150754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

30484

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000234

AC:

AN:

1111306

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

535784

show subpopulations

African (AFR)

AF:

0.000852

AC:

AN:

22310

American (AMR)

AF:

0.00

AC:

AN:

12408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15802

East Asian (EAS)

AF:

0.00

AC:

AN:

23538

South Asian (SAS)

AF:

0.00

AC:

AN:

35072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3006

European-Non Finnish (NFE)

AF:

0.00000751

AC:

AN:

932594

Other (OTH)

AF:

0.00

AC:

AN:

43468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000245

AC:

AN:

150754

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

73560

show subpopulations

African (AFR)

AF:

0.000872

AC:

AN:

41300

American (AMR)

AF:

0.00

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67524

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.000272

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Baller-Gerold syndrome (1)

Inborn genetic diseases (1)

RECQL4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.6

(source)

DANN

Benign

0.97

PhyloP100

-0.31

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

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

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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