19-13882896-C-T

Variant names:

• chr19-13882896-C-T
• rs111386677
• NM_001345843.2:c.1913G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001345843.2(BRME1):​c.1913G>A​(p.Arg638Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,613,752 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (47 hom.)
• Consequence: BRME1 NM_001345843.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60
• Publications: 12 publications found

Genes affected

BRME1 (HGNC:28153): (break repair meiotic recombinase recruitment factor 1) Predicted to be involved in meiosis I and spermatogenesis. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051855147).
• BP6: Variant 19-13882896-C-T is Benign according to our data. Variant chr19-13882896-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001345843.2. 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
	BRME1	NM_001345843.2	MANE Select	c.1913G>A	p.Arg638Gln	missense	Exon 9 of 9	NP_001332772.2	Q0VDD7-1
	BRME1	NM_001393645.1		c.1913G>A	p.Arg638Gln	missense	Exon 9 of 9	NP_001380574.1	Q0VDD7-1
	BRME1	NM_001393646.1		c.1913G>A	p.Arg638Gln	missense	Exon 10 of 10	NP_001380575.1	Q0VDD7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRME1	ENST00000586783.6	TSL:5 MANE Select	c.1913G>A	p.Arg638Gln	missense	Exon 9 of 9	ENSP00000465822.1	Q0VDD7-1
	BRME1	ENST00000871176.1		c.1913G>A	p.Arg638Gln	missense	Exon 9 of 9	ENSP00000541235.1
	BRME1	ENST00000871178.1		c.1913G>A	p.Arg638Gln	missense	Exon 9 of 9	ENSP00000541237.1

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 664 AN: 151880 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00545

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.00337

GnomAD2 exomes AF: 0.00428 AC: 1069 AN: 249620 AF XY: 0.00422

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00371

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00314

Gnomad NFE exome AF: 0.00721

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00668 AC: 9761 AN: 1461754 Hom.: 47 Cov.: 32 AF XY: 0.00645 AC XY: 4691 AN XY: 727166

African (AFR) AF: 0.00161 AC: 54 AN: 33478

American (AMR) AF: 0.00376 AC: 168 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26132

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.000997 AC: 86 AN: 86244

European-Finnish (FIN) AF: 0.00333 AC: 178 AN: 53414

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5738

European-Non Finnish (NFE) AF: 0.00800 AC: 8896 AN: 1111962

Other (OTH) AF: 0.00606 AC: 366 AN: 60392

GnomAD4 genome AF: 0.00437 AC: 664 AN: 151998 Hom.: 2 Cov.: 32 AF XY: 0.00408 AC XY: 303 AN XY: 74298

African (AFR) AF: 0.00128 AC: 53 AN: 41444

American (AMR) AF: 0.00544 AC: 83 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4814

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00722 AC: 491 AN: 67964

Other (OTH) AF: 0.00333 AC: 7 AN: 2100

Alfa AF: 0.00620 Hom.: 9

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00767 AC: 66

ExAC AF: 0.00458 AC: 556

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00646

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.050	T
Polyphen		0.75	P
Vest4		0.14
MVP		0.42
MPC		0.19
ClinPred		0.023	T
GERP RS		3.8
Varity_R		0.38
gMVP		0.021
Mutation Taster		=100/0	polymorphism

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: rs111386677; hg19: chr19-13993709; COSMIC: COSV59249223; COSMIC: COSV59249223;