chr11-27673917-A-G

Variant names:

• chr11-27673917-A-G
• rs11030108
• NM_001709.5:c.-21-15332T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001709.5(BDNF):​c.-21-15332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 976,550 control chromosomes in the GnomAD database, including 246,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40334 hom., cov: 31)
  • Exomes 𝑓: 0.70 (206569 hom.)
• Consequence: BDNF NM_001709.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.517
• Publications: 29 publications found

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-AS (HGNC:20608): (BDNF antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-27673917-A-G is Benign according to our data. Variant chr11-27673917-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDNF	NM_001709.5	c.-21-15332T>C		intron_variant	Intron 1 of 1	ENST00000356660.9	NP_001700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDNF	ENST00000356660.9	c.-21-15332T>C		intron_variant	Intron 1 of 1	1	NM_001709.5	ENSP00000349084.4
BDNF	ENST00000533131.5	c.-21-15332T>C		intron_variant	Intron 1 of 1	1		ENSP00000432727.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110257 AN: 151846 Hom.: 40313 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.703 AC: 580001 AN: 824586 Hom.: 206569 AF XY: 0.703 AC XY: 289105 AN XY: 411006

African (AFR) AF: 0.758 AC: 14657 AN: 19334

American (AMR) AF: 0.778 AC: 14604 AN: 18782

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 12869 AN: 15696

East Asian (EAS) AF: 0.966 AC: 31598 AN: 32726

South Asian (SAS) AF: 0.637 AC: 28056 AN: 44026

European-Finnish (FIN) AF: 0.667 AC: 24070 AN: 36060

Middle Eastern (MID) AF: 0.798 AC: 2376 AN: 2978

European-Non Finnish (NFE) AF: 0.688 AC: 424233 AN: 616860

Other (OTH) AF: 0.722 AC: 27538 AN: 38124

GnomAD4 genome AF: 0.726 AC: 110326 AN: 151964 Hom.: 40334 Cov.: 31 AF XY: 0.728 AC XY: 54052 AN XY: 74274

African (AFR) AF: 0.752 AC: 31159 AN: 41410

American (AMR) AF: 0.759 AC: 11587 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2848 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4905 AN: 5170

South Asian (SAS) AF: 0.647 AC: 3109 AN: 4806

European-Finnish (FIN) AF: 0.668 AC: 7040 AN: 10546

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47169 AN: 67980

Other (OTH) AF: 0.733 AC: 1549 AN: 2112

Alfa AF: 0.714 Hom.: 66904

Bravo AF: 0.736

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.39
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11030108; hg19: chr11-27695464;