Genetic Variant REC114:c.-4G>A (chr15-73443182-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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 (no stars).

Frequency

Genomes: 𝑓 0.028 ( 104 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1053 hom. )

Consequence

REC114
NM_001042367.2 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.00

Variant links:

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]

REC114 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
REC114	NM_001042367.2 link	c.-4G>A		5_prime_UTR_variant	Exon 1 of 6	ENST00000331090.11	NP_001035826.1
REC114	NM_001348772.2 link	c.-4G>A		5_prime_UTR_variant	Exon 1 of 5		NP_001335701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REC114	ENST00000331090 link	c.-4G>A		5_prime_UTR_variant	Exon 1 of 6	1	NM_001042367.2	ENSP00000328423.6		Q7Z4M0
REC114	ENST00000560581 link	c.-4G>A		5_prime_UTR_variant	Exon 1 of 5	2		ENSP00000452908.1		H0YKR2

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4270

AN:

152194

Hom.:

103

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0350

AC XY:

24356

AN XY:

695542

show subpopulations

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.:

AF XY:

0.0272

AC XY:

2027

AN XY:

74480

show subpopulations

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.:

Bravo

AF:

0.0300

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

REC114-related disorder

Benign:1

Apr 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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