chr17-75645819-G-A

Variant names:

• chr17-75645819-G-A
• rs4789223
• NM_004259.7:c.1229+5367C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

RECQL5 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• coronary artery disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004259.7. 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
	RECQL5	NM_004259.7	MANE Select	c.1229+5367C>T		intron	N/A	NP_004250.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL5	ENST00000317905.10	TSL:1 MANE Select	c.1229+5367C>T		intron	N/A	ENSP00000317636.5
	RECQL5	ENST00000423245.6	TSL:1	c.1148+5367C>T		intron	N/A	ENSP00000394820.2
	RECQL5	ENST00000919295.1		c.1229+5367C>T		intron	N/A	ENSP00000589354.1

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

African (AFR) AF: 0.207 AC: 8576 AN: 41506

American (AMR) AF: 0.490 AC: 7486 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2224 AN: 5164

South Asian (SAS) AF: 0.516 AC: 2483 AN: 4812

European-Finnish (FIN) AF: 0.588 AC: 6222 AN: 10578

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40796 AN: 67944

Other (OTH) AF: 0.481 AC: 1015 AN: 2110

Alfa AF: 0.540 Hom.: 28382

Bravo AF: 0.445

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		0.25
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4789223; hg19: chr17-73641899;