ENST00000621189.4:c.-1129G>T

Variant names:

• chr8-144517777-C-A
• rs979012066
• ENST00000621189.4:c.-1129G>T

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
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: -0.131
• Publications: 0 publications found

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]

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]

ACMG classification

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

Sel.	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

Sel.	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: 44 AN: 150724 Hom.: 0 Cov.: 34

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: 1 AN: 25200 AF XY: 0.00

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: 21 AN: 1088104 Hom.: 0 Cov.: 32 AF XY: 0.0000173 AC XY: 9 AN XY: 521510

African (AFR) AF: 0.000684 AC: 15 AN: 21940

American (AMR) AF: 0.000182 AC: 2 AN: 10996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15136

East Asian (EAS) AF: 0.00 AC: 0 AN: 23046

South Asian (SAS) AF: 0.00 AC: 0 AN: 30196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2930

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919428

Other (OTH) AF: 0.0000942 AC: 4 AN: 42446

GnomAD4 genome AF: 0.000292 AC: 44 AN: 150832 Hom.: 0 Cov.: 34 AF XY: 0.000394 AC XY: 29 AN XY: 73664

African (AFR) AF: 0.000990 AC: 41 AN: 41408

American (AMR) AF: 0.000198 AC: 3 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67496

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Baller-Gerold syndrome (1)
-	1	-	not provided (1)
-	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	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.22	T
PhyloP100		-0.13
PrimateAI	Pathogenic	0.88	D
Sift4G	Uncertain	0.017	D
PromoterAI		-0.0067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.27
gMVP		0.16
Mutation Taster		=78/22	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs979012066;

hg19: chr8-145743161;