rs12423412

Positions:

• chr12-21499707-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002907.4(RECQL):​c.-45-92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 623,600 control chromosomes in the GnomAD database, including 17,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3283 hom., cov: 33)
  • Exomes 𝑓: 0.24 (13964 hom.)
• Consequence: RECQL NM_002907.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.400

Genes affected

RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-21499707-G-A is Benign according to our data. Variant chr12-21499707-G-A is described in ClinVar as [Benign]. Clinvar id is 679679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4	c.-45-92C>T		intron_variant		ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7	c.-45-92C>T		intron_variant		2	NM_002907.4	ENSP00000416739	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28632 AN: 151984 Hom.: 3279 Cov.: 33

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.236 AC: 111172 AN: 471498 Hom.: 13964 AF XY: 0.237 AC XY: 59189 AN XY: 249480

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.188 AC: 28640 AN: 152102 Hom.: 3283 Cov.: 33 AF XY: 0.191 AC XY: 14228 AN XY: 74356

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.204

Alfa AF: 0.210 Hom.: 605

Bravo AF: 0.184

Asia WGS AF: 0.306 AC: 1064 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.64

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: rs12423412; hg19: chr12-21652641;