rs1554905164

Variant names:

• chr8-144517758-C-T
• rs1554905164
• NM_004260.4:c.27G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004260.4(RECQL4):​c.27G>A​(p.Glu9Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.686
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-144517758-C-T is Benign according to our data. Variant chr8-144517758-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 529107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.686 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. 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.27G>A	p.Glu9Glu	synonymous	Exon 1 of 21	NP_004251.4	O94761
	RECQL4	NM_001413019.1		c.27G>A	p.Glu9Glu	synonymous	Exon 1 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.27G>A	p.Glu9Glu	synonymous	Exon 1 of 21	NP_001399965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.27G>A	p.Glu9Glu	synonymous	Exon 1 of 21	ENSP00000482313.2	O94761
	RECQL4	ENST00000621189.4	TSL:1	c.-1110G>A		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1	A0A087X072
	RECQL4	ENST00000971710.1		c.27G>A	p.Glu9Glu	synonymous	Exon 1 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1162812 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 565854

African (AFR) AF: 0.00 AC: 0 AN: 23208

American (AMR) AF: 0.00 AC: 0 AN: 15416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17428

East Asian (EAS) AF: 0.00 AC: 0 AN: 24674

South Asian (SAS) AF: 0.00 AC: 0 AN: 45562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3206

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 961138

Other (OTH) AF: 0.00 AC: 0 AN: 46250

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Baller-Gerold syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.3
DANN	Benign	0.93
PhyloP100		-0.69
PromoterAI		-0.090	Neutral

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: rs1554905164; hg19: chr8-145743142;