rs200941778

Variant names:

• chr8-144515368-C-G
• NM_004260.4:c.1348G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144515368-C-G
• chr8-144515368-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001413043.1(RECQL4):​c.-120G>C 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 0.000000685 in 1,460,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RECQL4 NM_001413043.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15927348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1348G>C	p.Val450Leu	missense_variant	Exon 7 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1348G>C	p.Val450Leu	missense_variant	Exon 7 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.277G>C	p.Val93Leu	missense_variant	Exon 6 of 20	1		ENSP00000483145.1
RECQL4	ENST00000532846.2	c.232G>C	p.Val78Leu	missense_variant	Exon 3 of 9	5		ENSP00000476551.1
RECQL4	ENST00000688394.1	n.371G>C		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460374 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	1.7
DANN	Benign	0.53
DEOGEN2	Benign	0.021	T;T
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T;T
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.17	T;T
Polyphen		0.38	.;B
Vest4		0.22
MVP		0.51
GERP RS		-0.75
Varity_R		0.050
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145740752;