rs1001894022

Variant names:

• chr8-144517756-C-A
• rs1001894022
• ENST00000621189.4:c.-1108G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144517756-C-A
• chr8-144517756-C-G
• chr8-144517756-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001413023.1(RECQL4):​c.-1108G>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 0.000000861 in 1,161,240 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: not found (cov: 34)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: RECQL4 NM_001413023.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.68
• 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: 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=0.07349345).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.29G>T	p.Arg10Leu	missense	Exon 1 of 21	NP_004251.4
	RECQL4	NM_001413023.1		c.-1108G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001399952.1
	RECQL4	NM_001413041.1		c.-1170G>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.-1108G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000483145.1
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.29G>T	p.Arg10Leu	missense	Exon 1 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.-1108G>T		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.61e-7 AC: 1 AN: 1161240 Hom.: 0 Cov.: 32 AF XY: 0.00000177 AC XY: 1 AN XY: 564854

African (AFR) AF: 0.00 AC: 0 AN: 23178

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17330

East Asian (EAS) AF: 0.00 AC: 0 AN: 24648

South Asian (SAS) AF: 0.0000221 AC: 1 AN: 45194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 960412

Other (OTH) AF: 0.00 AC: 0 AN: 46170

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	0.23
DANN	Benign	0.76
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.073	T
PhyloP100		-3.7
PrimateAI	Pathogenic	0.82	D
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.14
MVP		0.66
GERP RS		-0.60
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.15
gMVP		0.093
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs1001894022; hg19: chr8-145743140;