19-13905961-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001345843.2(BRME1):​c.-268C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 149,260 control chromosomes in the GnomAD database, including 8,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 8030 hom., cov: 30)
Exomes 𝑓: 0.32 ( 10 hom. )

Consequence

BRME1
NM_001345843.2 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

Publications

5 publications found
Variant links:
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]
CC2D1A (HGNC:30237): (coiled-coil and C2 domain containing 1A) This gene encodes a transcriptional repressor that binds to a conserved 14-bp 5'-repressor element and regulates expression of the 5-hydroxytryptamine (serotonin) receptor 1A gene in neuronal cells. The DNA binding and transcriptional repressor activities of the protein are inhibited by calcium. A mutation in this gene results in a nonsyndromic form of cognitive disability (MRT3). [provided by RefSeq, Jul 2017]
CC2D1A Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • intellectual disability, autosomal recessive 3
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • autosomal recessive non-syndromic intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRME1NM_001345843.2 linkc.-268C>T 5_prime_UTR_variant Exon 1 of 9 ENST00000586783.6 NP_001332772.2
CC2D1ANM_017721.5 linkc.-481G>A upstream_gene_variant ENST00000318003.11 NP_060191.3 Q6P1N0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRME1ENST00000586783.6 linkc.-268C>T 5_prime_UTR_variant Exon 1 of 9 5 NM_001345843.2 ENSP00000465822.1 Q0VDD7-1
CC2D1AENST00000318003.11 linkc.-481G>A upstream_gene_variant 1 NM_017721.5 ENSP00000313601.6 Q6P1N0-1

Frequencies

GnomAD3 genomes
AF:
0.307
AC:
45680
AN:
148952
Hom.:
8001
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.546
Gnomad AMI
AF:
0.107
Gnomad AMR
AF:
0.247
Gnomad ASJ
AF:
0.142
Gnomad EAS
AF:
0.280
Gnomad SAS
AF:
0.288
Gnomad FIN
AF:
0.165
Gnomad MID
AF:
0.177
Gnomad NFE
AF:
0.219
Gnomad OTH
AF:
0.269
GnomAD4 exome
AF:
0.325
AC:
63
AN:
194
Hom.:
10
Cov.:
0
AF XY:
0.268
AC XY:
30
AN XY:
112
show subpopulations
African (AFR)
AF:
0.563
AC:
9
AN:
16
American (AMR)
AF:
0.750
AC:
3
AN:
4
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
0.300
AC:
3
AN:
10
South Asian (SAS)
AF:
0.250
AC:
5
AN:
20
European-Finnish (FIN)
AF:
0.167
AC:
2
AN:
12
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.293
AC:
34
AN:
116
Other (OTH)
AF:
0.438
AC:
7
AN:
16
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.526
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.307
AC:
45757
AN:
149066
Hom.:
8030
Cov.:
30
AF XY:
0.302
AC XY:
22001
AN XY:
72888
show subpopulations
African (AFR)
AF:
0.546
AC:
21478
AN:
39336
American (AMR)
AF:
0.247
AC:
3736
AN:
15134
Ashkenazi Jewish (ASJ)
AF:
0.142
AC:
491
AN:
3456
East Asian (EAS)
AF:
0.279
AC:
1411
AN:
5052
South Asian (SAS)
AF:
0.287
AC:
1354
AN:
4722
European-Finnish (FIN)
AF:
0.165
AC:
1738
AN:
10522
Middle Eastern (MID)
AF:
0.197
AC:
58
AN:
294
European-Non Finnish (NFE)
AF:
0.219
AC:
14823
AN:
67552
Other (OTH)
AF:
0.273
AC:
571
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1325
2650
3975
5300
6625
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
440
880
1320
1760
2200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.279
Hom.:
714
Asia WGS
AF:
0.351
AC:
1219
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
6.5
DANN
Benign
0.83
PhyloP100
0.022
PromoterAI
0.0092
Neutral
Mutation Taster
=300/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs3745457; hg19: chr19-14016774; API