Genetic Variant ENST00000532997.5:c.-56C>T (chr11-27719545-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000532997.5(BDNF):c.-56C>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 0.455 in 984,812 control chromosomes in the GnomAD database, including 104,789 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 0.41 ( 13988 hom., cov: 29)

Exomes 𝑓: 0.46 ( 90801 hom. )

Consequence

BDNF
ENST00000532997.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.912

Publications

23 publications found

Variant links:

Genes affected

BDNF (HGNC:1033): (brain derived neurotrophic factor) This gene encodes a member of the nerve growth factor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain. Expression of this gene is reduced in Alzheimer's, Parkinson's, and Huntington's disease patients. This gene may play a role in the regulation of the stress response and in the biology of mood disorders. [provided by RefSeq, Nov 2015]

BDNF links:

ENSG00000255496 (HGNC:):

ENSG00000255496 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532997.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
BDNF	NM_001143807.2	c.-56C>T	5_prime_UTR	Exon 1 of 2	NP_001137279.1	A0A0E3SU01
BDNF	NM_170731.5	c.3+1867C>T	intron	N/A	NP_733927.1	P23560-2
BDNF	NM_001143805.1	c.-22+1099C>T	intron	N/A	NP_001137277.1	P23560-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BDNF	ENST00000532997.5	TSL:1	c.-56C>T	5_prime_UTR	Exon 1 of 2	ENSP00000435805.1	P23560-1
BDNF	ENST00000314915.6	TSL:1	c.3+1867C>T	intron	N/A	ENSP00000320002.6	P23560-2
BDNF	ENST00000395978.7	TSL:1	c.-22+884C>T	intron	N/A	ENSP00000379302.3	P23560-1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61801

AN:

151492

Hom.:

13987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.429

GnomAD4 exome

AF:

0.464

AC:

386611

AN:

833200

Hom.:

90801

Cov.:

AF XY:

0.464

AC XY:

178628

AN XY:

384802

show subpopulations

African (AFR)

AF:

0.190

AC:

3002

AN:

15786

American (AMR)

AF:

0.575

AC:

566

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

2668

AN:

5154

East Asian (EAS)

AF:

0.456

AC:

1656

AN:

3632

South Asian (SAS)

AF:

0.332

AC:

5459

AN:

16460

European-Finnish (FIN)

AF:

0.460

AC:

127

AN:

276

Middle Eastern (MID)

AF:

0.490

AC:

795

AN:

1624

European-Non Finnish (NFE)

AF:

0.472

AC:

359750

AN:

761972

Other (OTH)

AF:

0.461

AC:

12588

AN:

27312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12437

24874

37310

49747

62184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14518

29036

43554

58072

72590

<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:

0.408

AC:

61811

AN:

151612

Hom.:

13988

Cov.:

AF XY:

0.411

AC XY:

30441

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.211

AC:

8712

AN:

41366

American (AMR)

AF:

0.527

AC:

8026

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1779

AN:

3466

East Asian (EAS)

AF:

0.444

AC:

2268

AN:

5108

South Asian (SAS)

AF:

0.333

AC:

1594

AN:

4792

European-Finnish (FIN)

AF:

0.490

AC:

5137

AN:

10494

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.484

AC:

32832

AN:

67838

Other (OTH)

AF:

0.430

AC:

905

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1678

3356

5035

6713

8391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.335

Hom.:

1015

Bravo

AF:

0.403

Asia WGS

AF:

0.365

AC:

1272

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.91

PromoterAI

0.0028

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over