dbSNP rs368989729: RECQL4:p.Arg848Leu (chr8-144513059-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004260.4(RECQL4):c.2543G>T(p.Arg848Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R848H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

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:

ENSG00000265393 (HGNC:):

ENSG00000265393 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10761374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.2543G>T	p.Arg848Leu	missense_variant	Exon 15 of 21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RECQL4	ENST00000617875.6 link	c.2543G>T	p.Arg848Leu	missense_variant	Exon 15 of 21	1	NM_004260.4	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4 link	c.1472G>T	p.Arg491Leu	missense_variant	Exon 14 of 20	1		ENSP00000483145.1	A0A087X072
RECQL4	ENST00000534626.6 link	c.713G>T	p.Arg238Leu	missense_variant	Exon 6 of 8	5		ENSP00000477457.1	V9GZ64
ENSG00000265393	ENST00000580385.1 link	n.271+222C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1427338

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

706894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32786

American (AMR)

AF:

0.00

AC:

AN:

39900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25034

East Asian (EAS)

AF:

0.00

AC:

AN:

37918

South Asian (SAS)

AF:

0.00

AC:

AN:

81898

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095634

Other (OTH)

AF:

0.00

AC:

AN:

59056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.6

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.075

T;T

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

T;T

MutationAssessor

Benign

1.7

.;L

PhyloP100

-1.1

PrimateAI

Benign

0.28

Sift4G

Uncertain

0.042

D;D

Polyphen

0.12

.;B

Vest4

0.13

MVP

0.73

GERP RS

-0.48

PromoterAI

0.028

Neutral

(source)

Varity_R

0.14

gMVP

0.55

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over