15-73443182-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001042367.2(REC114):c.-4G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 1,560,260 control chromosomes in the GnomAD database, including 1,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (104 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1053 hom.)
• Consequence: REC114 NM_001042367.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00

Genes affected

REC114 (HGNC:25065): (REC114 meiotic recombination protein) The protein encoded by this gene is orthologous to the mouse meiotic recombination protein REC114, which is involved in DNA double-strand break formation during meiosis. The encoded protein is conserved in most eukaryotes and was first discovered and characterized in yeast. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-73443182-G-A is Benign according to our data. Variant chr15-73443182-G-A is described in ClinVar as [Benign]. Clinvar id is 3059656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REC114	NM_001042367.2	c.-4G>A		5_prime_UTR_variant	1/6	ENST00000331090.11
REC114	NM_001348772.2	c.-4G>A		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REC114	ENST00000331090.11	c.-4G>A		5_prime_UTR_variant	1/6	1	NM_001042367.2	P1
REC114	ENST00000560581.1	c.-4G>A		5_prime_UTR_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4270 AN: 152194 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.0497

GnomAD3 exomes AF: 0.0310 AC: 5199 AN: 167836 Hom.: 129 AF XY: 0.0311 AC XY: 2791 AN XY: 89718

Gnomad AFR exome AF: 0.00537

Gnomad AMR exome AF: 0.0323

Gnomad ASJ exome AF: 0.0894

Gnomad EAS exome AF: 0.000247

Gnomad SAS exome AF: 0.0169

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0395

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0353 AC: 49649 AN: 1407948 Hom.: 1053 Cov.: 31 AF XY: 0.0350 AC XY: 24356 AN XY: 695542

Gnomad4 AFR exome AF: 0.00687

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.0914

Gnomad4 EAS exome AF: 0.000219

Gnomad4 SAS exome AF: 0.0176

Gnomad4 FIN exome AF: 0.00952

Gnomad4 NFE exome AF: 0.0381

Gnomad4 OTH exome AF: 0.0372

GnomAD4 genome AF: 0.0280 AC: 4270 AN: 152312 Hom.: 104 Cov.: 32 AF XY: 0.0272 AC XY: 2027 AN XY: 74480

Gnomad4 AFR AF: 0.00700

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.00734

Gnomad4 NFE AF: 0.0409

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0368 Hom.: 66

Bravo AF: 0.0300

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

REC114-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.14
Dann	Benign	0.88

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: rs72741460; hg19: chr15-73735523;