rs4789223

Positions:

• chr17-75645819-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004259.7(RECQL5):​c.1229+5367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,082 control chromosomes in the GnomAD database, including 18,871 homozygotes. 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: 𝑓 0.47 (18871 hom., cov: 32)
• Consequence: RECQL5 NM_004259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

Genes affected

RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL5	NM_004259.7	c.1229+5367C>T		intron_variant		ENST00000317905.10
RECQL5	XM_005257818.5	c.1229+5367C>T		intron_variant
RECQL5	XM_047437085.1	c.1229+5367C>T		intron_variant
RECQL5	XM_047437091.1	c.1229+5367C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL5	ENST00000317905.10	c.1229+5367C>T		intron_variant		1	NM_004259.7	P1
RECQL5	ENST00000423245.6	c.1148+5367C>T		intron_variant		1
RECQL5	ENST00000578201.5	c.1229+5367C>T		intron_variant		5
RECQL5	ENST00000582464.5	c.*123+4698C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71141 AN: 151964 Hom.: 18864 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.468 AC: 71160 AN: 152082 Hom.: 18871 Cov.: 32 AF XY: 0.469 AC XY: 34872 AN XY: 74340

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.481

Alfa AF: 0.556 Hom.: 22586

Bravo AF: 0.445

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs4789223; hg19: chr17-73641899;