Genetic Variant RECQL5:c.2875+6C>T (chr17-75627617-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004259.7(RECQL5):c.2875+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,613,272 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 12 hom. )

Consequence

RECQL5
NM_004259.7 splice_region, intron

Scores

Splicing: ADA: 0.00001522

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.815

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-75627617-G-A is Benign according to our data. Variant chr17-75627617-G-A is described in ClinVar as [Benign]. Clinvar id is 721351.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL5	NM_004259.7 link	c.2875+6C>T		splice_region_variant, intron_variant	Intron 19 of 19	ENST00000317905.10	NP_004250.4	O94762-1A0A024R8M9Q8WYH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL5	ENST00000317905.10 link	c.2875+6C>T		splice_region_variant, intron_variant	Intron 19 of 19	1	NM_004259.7	ENSP00000317636.5		O94762-1
RECQL5	ENST00000423245.6 link	c.2794+6C>T		splice_region_variant, intron_variant	Intron 19 of 19	1		ENSP00000394820.2		O94762-4

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00150

AC:

370

AN:

245880

Hom.:

AF XY:

0.00134

AC XY:

179

AN XY:

133842

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.0310

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.000776

AC:

1134

AN:

1461044

Hom.:

Cov.:

AF XY:

0.000795

AC XY:

578

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000899

Gnomad4 ASJ exome

AF:

0.0293

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.000736

AC:

112

AN:

152228

Hom.:

Cov.:

AF XY:

0.000834

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.0262

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.000858

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.6

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.018

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over