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GeneBe

rs6265

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001709(BDNF):c.196G>A(p.Val66Met) variant causes a missense change. The variant allele was found at a frequency of 0.153 in 152064 control chromosomes in the gnomAD Genomes database, including 2519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (β˜…β˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2519 hom., cov: 32)
Exomes 𝑓: 0.19 ( 6030 hom. )

Consequence

BDNF
NM_001709 missense

Scores

1
7
9

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 4.94

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.0017960966).
BP6
?
Variant 11:27658369-C>T is Benign according to our data. Variant chr11-27658369-C-T is described in ClinVar as [Benign]. Clinvar id is 17697. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDNFNM_001709.5 linkuse as main transcriptc.196G>A p.Val66Met missense_variant 2/2 ENST00000356660.9
BDNF-ASNR_033312.1 linkuse as main transcriptn.434C>T non_coding_transcript_exon_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDNFENST00000356660.9 linkuse as main transcriptc.196G>A p.Val66Met missense_variant 2/21 NM_001709.5 P4P23560-1
BDNF-ASENST00000651238.1 linkuse as main transcriptn.508C>T non_coding_transcript_exon_variant 5/8

Frequencies

GnomAD3 genomes
AF:
0.153
AC:
23190
AN:
152064
Hom.:
2519
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0373
Gnomad AMI
AF:
0.335
Gnomad AMR
AF:
0.159
Gnomad ASJ
AF:
0.222
Gnomad EAS
AF:
0.473
Gnomad SAS
AF:
0.202
Gnomad FIN
AF:
0.151
Gnomad MID
AF:
0.146
Gnomad NFE
AF:
0.187
Gnomad OTH
AF:
0.170
GnomAD3 exomes
AF:
0.195
AC:
48968
AN:
251276
Hom.:
6030
AF XY:
0.199
AC XY:
26958
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.0333
Gnomad AMR exome
AF:
0.152
Gnomad ASJ exome
AF:
0.216
Gnomad EAS exome
AF:
0.492
Gnomad SAS exome
AF:
0.194
Gnomad FIN exome
AF:
0.152
Gnomad NFE exome
AF:
0.190
Gnomad OTH exome
AF:
0.183
GnomAD4 exome
AF:
0.190
AC:
277361
AN:
1461886
Hom.:
28821
AF XY:
0.191
AC XY:
138787
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0300
Gnomad4 AMR exome
AF:
0.148
Gnomad4 ASJ exome
AF:
0.218
Gnomad4 EAS exome
AF:
0.443
Gnomad4 SAS exome
AF:
0.192
Gnomad4 FIN exome
AF:
0.153
Gnomad4 NFE exome
AF:
0.188
Gnomad4 OTH exome
AF:
0.188
Alfa
AF:
0.189
Hom.:
7433
Bravo
AF:
0.151
TwinsUK
AF:
0.193
AC:
715
ALSPAC
AF:
0.180
AC:
693
ESP6500AA
AF:
0.0418
AC:
184
ESP6500EA
AF:
0.191
AC:
1640
ExAC
AF:
0.194
AC:
23513
Asia WGS
AF:
0.278
AC:
967
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJun 18, 2013Benign with respect to pulmonary disease based on high population frequency, Th is variant has been proposed to be associated with a rnage of psychiatric manife stations though the data is not solid and more recent meta-analyses argue agains t a risk effect. -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, PreventionGenetics-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 30, 2022- -
Memory impairment, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMDec 13, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.27
Cadd
Benign
18
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D;D;.;D;D;D;D;D;D;.;D;D;D;D;D;D;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.95
D
MetaRNN
Benign
0.0018
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.4
M;M;.;M;M;M;M;M;M;.;M;M;M;M;M;M;.
MutationTaster
Benign
9.8e-7
P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.72
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
0.23
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
1.0
D;D;D;D;D;D;D;D;D;P;D;D;D;D;D;D;D
Vest4
0.074
MPC
1.6
ClinPred
0.026
T
GERP RS
5.3
Varity_R
0.22
gMVP
0.66

Splicing

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.

Other links and lift over

dbSNP: rs6265; hg19: chr11-27679916; COSMIC: COSV59234714; COSMIC: COSV59234714;